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Miller BM, Goessling W. Distribution and developmental timing of zebrafish liver innervation. Biol Lett 2024; 20:20240288. [PMID: 39163983 PMCID: PMC11335395 DOI: 10.1098/rsbl.2024.0288] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/06/2024] [Revised: 06/27/2024] [Accepted: 06/28/2024] [Indexed: 08/22/2024] Open
Abstract
Hepatic innervation regulates multiple aspects of liver function, repair and regeneration, and liver denervation is associated with higher rates of metabolic disorders in humans. However, the mechanisms regulating the development of the hepatic nervous system, as well as the role of the hepatic nervous system in liver development and maturation, are still largely unknown. Zebrafish are a widely used model of liver development and regeneration, but hepatic innervation in zebrafish has not yet been described in detail. Here, we examine the extent and developmental timing of hepatic innervation in zebrafish. We demonstrate that innervation is restricted to large bile ducts and blood vessels in both juvenile and adult zebrafish livers, as we find no evidence for direct innervation of hepatocytes. Innervation contacting the periphery of the liver is visible as early as 72 h post-fertilization, while intrahepatic innervation is not established until 21 days post-fertilization. Therefore, zebrafish hepatic innervation resembles that of previously examined fish species, making them an excellent model to investigate both the role of the hepatic nervous system during liver maturation and the mechanisms governing the elaboration of the intrahepatic nerve network between fish and mammals.
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Affiliation(s)
- Bess M. Miller
- Division of Genetics, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA02115, USA
| | - Wolfram Goessling
- Division of Genetics, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA02115, USA
- Broad Institute of MIT and Harvard, Cambridge, MA02142, USA
- Harvard Stem Cell Institute, Cambridge, MA02138, USA
- Division of Health Sciences and Technology, Harvard-MIT, Cambridge, MA02139, USA
- Division of Gastroenterology, Massachusetts General Hospital, Boston, MA02114, USA
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Shiojiri N, Hirose H, Ota N, Sekiguchi J, Matsubara S, Kawakami H. Changes of biliary cilia, smooth muscle tissue distribution, innervation and extracellular matrices during morphological evolution of hepatic architectures in vertebrates. Ann Anat 2023; 250:152148. [PMID: 37591347 DOI: 10.1016/j.aanat.2023.152148] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/08/2023] [Revised: 07/10/2023] [Accepted: 07/31/2023] [Indexed: 08/19/2023]
Abstract
BACKGROUND The liver architecture of vertebrates can be classified into two types, the portal triad type (having periportal bile ducts) and the non-portal triad type (having bile ducts independent of the course of portal veins). The former is typically detectable in livers of tetrapods and cartilaginous fish, and its ancestral state is found in the hagfish, an earliest diverged lineage among vertebrates. Teleosts other than osteoglossomorphs have the latter. The aim of the present study is to reveal the changes of the hepatic innervation, biliary cilia and smooth muscle distribution, and extracellular matrices along vertebrate evolution with attention to the two types of liver architectures. METHODS The hepatic innervation, biliary cilia and smooth muscle distribution, and collagen deposition were immunohistochemically and histochemically compared among livers of various vertebrates, using anti-acetylated tubulin and anti-α-smooth muscle actin antibodies, and Sirius red staining. These were also ultrastructurally examined. RESULTS Although the hagfish liver had periportal intrahepatic bile ducts and ductules as detected in mammalian livers, it lacked smooth muscles around bile ducts and portal veins. Extracellular matrices in their connective tissues had thick collagen fibers. Its innervation was restricted to intrahepatic bile ducts and portal veins in the hilum. In livers of other vertebrates, including teleosts, the innervation was broadly detectable, especially around bile ducts, hepatic arteries and portal veins (afferent vessels), but not around central veins (efferent vessels). The chondrichthyans ultrastructurally had smooth muscle tissue around bile ducts. Cilia distribution was confirmed in intrahepatic bile ducts of tetrapods and basal actinopterygians. Teleosts other than osteoglossomorphs lacked cilia in their intrahepatic bile ducts. CONCLUSIONS The liver architecture of the hagfish may be unique for innervation and extracellular matrices. Hepatic innervation may not have occurred in vertebrate ancestors. Hepatic innervation in bile ducts, hepatic arteries and portal veins may have been conserved among the extant jawed vertebrates. Cilia distribution in bile ducts may have changed during evolution of actinopterygians.
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Affiliation(s)
- Nobuyoshi Shiojiri
- Department of Biology, Faculty of Science, Shizuoka University, 836 Oya, Suruga-ku, Shizuoka 422-8529, Japan; Graduate School of Science and Technology, Shizuoka University, 836 Oya, Suruga-ku, Shizuoka 422-8529, Japan.
| | - Haruka Hirose
- Department of Biology, Faculty of Science, Shizuoka University, 836 Oya, Suruga-ku, Shizuoka 422-8529, Japan
| | - Noriaki Ota
- Graduate School of Science and Technology, Shizuoka University, 836 Oya, Suruga-ku, Shizuoka 422-8529, Japan
| | - Junri Sekiguchi
- Laboratory for Electron Microscopy, Kyorin University School of Medicine, 6-20-2 Shinkawa, Mitaka-shi, Tokyo 181-8611, Japan; Department of Anatomy, Kyorin University School of Medicine, 6-20-2 Shinkawa, Mitaka-shi, Tokyo 181-8611, Japan
| | - Sachie Matsubara
- Laboratory for Electron Microscopy, Kyorin University School of Medicine, 6-20-2 Shinkawa, Mitaka-shi, Tokyo 181-8611, Japan; Department of Anatomy, Kyorin University School of Medicine, 6-20-2 Shinkawa, Mitaka-shi, Tokyo 181-8611, Japan
| | - Hayato Kawakami
- Laboratory for Electron Microscopy, Kyorin University School of Medicine, 6-20-2 Shinkawa, Mitaka-shi, Tokyo 181-8611, Japan; Department of Anatomy, Kyorin University School of Medicine, 6-20-2 Shinkawa, Mitaka-shi, Tokyo 181-8611, Japan
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Koike N, Tadokoro T, Ueno Y, Okamoto S, Kobayashi T, Murata S, Taniguchi H. Development of the nervous system in mouse liver. World J Hepatol 2022; 14:386-399. [PMID: 35317173 PMCID: PMC8891673 DOI: 10.4254/wjh.v14.i2.386] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/31/2021] [Revised: 10/12/2021] [Accepted: 01/20/2022] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND The role of the hepatic nervous system in liver development remains unclear. We previously created functional human micro-hepatic tissue in mice by co-culturing human hepatic endodermal cells with endothelial and mesenchymal cells. However, they lacked Glisson’s sheath [the portal tract (PT)]. The PT consists of branches of the hepatic artery (HA), portal vein, and intrahepatic bile duct (IHBD), collectively called the portal triad, together with autonomic nerves.
AIM To evaluate the development of the mouse hepatic nervous network in the PT using immunohistochemistry.
METHODS Liver samples from C57BL/6J mice were harvested at different developmental time periods, from embryonic day (E) 10.5 to postnatal day (P) 56. Thin sections of the surface cut through the hepatic hilus were examined using protein gene product 9.5 (PGP9.5) and cytokeratin 19 (CK19) antibodies, markers of nerve fibers (NFs), and biliary epithelial cells (BECs), respectively. The numbers of NFs and IHBDs were separately counted in a PT around the hepatic hilus (center) and the peripheral area (periphery) of the liver, comparing the average values between the center and the periphery at each developmental stage. NF-IHBD and NF-HA contacts in a PT were counted, and their relationship was quantified. SRY-related high mobility group-box gene 9 (SOX9), another BEC marker; hepatocyte nuclear factor 4α (HNF4α), a marker of hepatocytes; and Jagged-1, a Notch ligand, were also immunostained to observe the PT development.
RESULTS HNF4α was expressed in the nucleus, and Jagged-1 was diffusely positive in the primitive liver at E10.5; however, the PGP9.5 and CK19 were negative in the fetal liver. SOX9-positive cells were scattered in the periportal area in the liver at E12.5. The Jagged-1 was mainly expressed in the periportal tissue, and the number of SOX9-positive cells increased at E16.5. SOX9-positive cells constructed the ductal plate and primitive IHBDs mainly at the center, and SOX-9-positive IHBDs partly acquired CK19 positivity at the same period. PGP9.5-positive bodies were first found at E16.5 and HAs were first found at P0 in the periportal tissue of the center. Therefore, primitive PT structures were first constructed at P0 in the center. Along with remodeling of the periportal tissue, the number of CK19-positive IHBDs and PGP9.5-positive NFs gradually increased, and PTs were also formed in the periphery until P5. The numbers of NFs and IHBDs were significantly higher in the center than in the periphery from E16.5 to P5. The numbers of NFs and IHBDs reached the adult level at P28, with decreased differences between the center and periphery. NFs associated more frequently with HAs than IHBDs in PTs at the early phase after birth, after which the number of NF-IHBD contacts gradually increased.
CONCLUSION Mouse hepatic NFs first emerge at the center just before birth and extend toward the periphery. The interaction between NFs and IHBDs or HAs plays important roles in the morphogenesis of PT structure.
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Affiliation(s)
- Naoto Koike
- Department of Surgery, Seirei Sakura Citizen Hospital, Sakura 285-8765, Chiba, Japan
- Department of Regenerative Medicine, Yokohama City University Graduate School of Medicine, Yokohama 236-0004, Kanagawa, Japan
| | - Tomomi Tadokoro
- Department of Regenerative Medicine, Yokohama City University Graduate School of Medicine, Yokohama 236-0004, Kanagawa, Japan
| | - Yasuharu Ueno
- Department of Regenerative Medicine, Yokohama City University Graduate School of Medicine, Yokohama 236-0004, Kanagawa, Japan
- Division of Regenerative Medicine, Center for Stem Cell Biology and Regenerative Medicine, The Institute of Medical Science, The University of Tokyo, Tokyo 108-8639, Japan
| | - Satoshi Okamoto
- Department of Regenerative Medicine, Yokohama City University Graduate School of Medicine, Yokohama 236-0004, Kanagawa, Japan
| | - Tatsuya Kobayashi
- Department of Regenerative Medicine, Yokohama City University Graduate School of Medicine, Yokohama 236-0004, Kanagawa, Japan
| | - Soichiro Murata
- Department of Regenerative Medicine, Yokohama City University Graduate School of Medicine, Yokohama 236-0004, Kanagawa, Japan
| | - Hideki Taniguchi
- Department of Regenerative Medicine, Yokohama City University Graduate School of Medicine, Yokohama 236-0004, Kanagawa, Japan
- Division of Regenerative Medicine, Center for Stem Cell Biology and Regenerative Medicine, The Institute of Medical Science, The University of Tokyo, Tokyo 108-8639, Japan
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Miller BM, Oderberg IM, Goessling W. Hepatic Nervous System in Development, Regeneration, and Disease. Hepatology 2021; 74:3513-3522. [PMID: 34256416 PMCID: PMC8639644 DOI: 10.1002/hep.32055] [Citation(s) in RCA: 22] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/12/2021] [Revised: 06/10/2021] [Accepted: 07/01/2021] [Indexed: 12/12/2022]
Abstract
The liver is innervated by autonomic and sensory fibers of the sympathetic and parasympathetic nervous systems that regulate liver function, regeneration, and disease. Although the importance of the hepatic nervous system in maintaining and restoring liver homeostasis is increasingly appreciated, much remains unknown about the specific mechanisms by which hepatic nerves both influence and are influenced by liver diseases. While recent work has begun to illuminate the developmental mechanisms underlying recruitment of nerves to the liver, evolutionary differences contributing to species-specific patterns of hepatic innervation remain elusive. In this review, we summarize current knowledge on the development of the hepatic nervous system and its role in liver regeneration and disease. We also highlight areas in which further investigation would greatly enhance our understanding of the evolution and function of liver innervation.
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Affiliation(s)
- Bess M. Miller
- Division of Genetics, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, 02115, USA
| | - Isaac M. Oderberg
- Division of Genetics, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, 02115, USA
| | - Wolfram Goessling
- Division of Genetics, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, 02115, USA.,Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.,Harvard Stem Cell Institute, Cambridge, MA, 02138, USA.,Harvard-MIT Division of Health Sciences and Technology, Cambridge, MA, 02139, USA.,Division of Gastroenterology, Massachusetts General Hospital, Boston, MA, 02114, USA.,corresponding author: Contact Information: Wolfram Goessling, MD, PhD, Wang 539B, 55 Fruit Street, Boston, MA 02114,
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Bisschop PH, Fliers E, Kalsbeek A. Autonomic Regulation of Hepatic Glucose Production. Compr Physiol 2014; 5:147-65. [DOI: 10.1002/cphy.c140009] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
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Yi CX, la Fleur SE, Fliers E, Kalsbeek A. The role of the autonomic nervous liver innervation in the control of energy metabolism. Biochim Biophys Acta Mol Basis Dis 2010; 1802:416-31. [PMID: 20060897 DOI: 10.1016/j.bbadis.2010.01.006] [Citation(s) in RCA: 156] [Impact Index Per Article: 10.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/15/2009] [Revised: 12/04/2009] [Accepted: 01/05/2010] [Indexed: 01/13/2023]
Abstract
Despite a longstanding research interest ever since the early work by Claude Bernard, the functional significance of autonomic liver innervation, either sympathetic or parasympathetic, is still ill defined. This scarcity of information not only holds for the brain control of hepatic metabolism, but also for the metabolic sensing function of the liver and the way in which this metabolic information from the liver affects the brain. Clinical information from the bedside suggests that successful human liver transplantation (implying a complete autonomic liver denervation) causes no life threatening metabolic derangements, at least in the absence of severe metabolic challenges such as hypoglycemia. However, from the benchside, data are accumulating that interference with the neuronal brain-liver connection does cause pronounced changes in liver metabolism. This review provides an extensive overview on how metabolic information is sensed by the liver, and how this information is processed via neuronal pathways to the brain. With this information the brain controls liver metabolism and that of other organs and tissues. We will pay special attention to the hypothalamic pathways involved in these liver-brain-liver circuits. At this stage, we still do not know the final destination and processing of the metabolic information that is transferred from the liver to the brain. On the other hand, in recent years, there has been a considerable increase in the understanding which brain areas are involved in the control of liver metabolism via its autonomic innervation. However, in view of the ever rising prevalence of type 2 diabetes, this potentially highly relevant knowledge is still by far too limited. Thus the autonomic innervation of the liver and its role in the control of metabolism needs our continued and devoted attention.
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Affiliation(s)
- Chun-Xia Yi
- Hypothalamic Integration Mechanisms, Netherlands Institute for Neuroscience, Amsterdam, The Netherlands
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Xu CS, Yuan JY, Li WQ, Han HP, Yang KJ, Chang CF, Zhao LF, Li YC, Zhang HY, Rahman S, Zhang JB. Identification of expressed genes in regenerating rat liver in 0-4-8-12 h short interval successive partial hepatectomy. World J Gastroenterol 2005; 11:2296-305. [PMID: 15818742 PMCID: PMC4305815 DOI: 10.3748/wjg.v11.i15.2296] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
AIM: To identify the genes differentially expressed in the regenerating rat liver of 0-4-8-12 h short interval successive partial hepatectomy (SISPH) and to analyze their expression profiles.
METHODS: Five hundred and fifty-one elements screened from subtractive cDNA libraries were made into a cDNA microarray (cDNA chip). Extensive gene expression analysis following 0-4-8-12 h SISPH was conducted by microarray.
RESULTS: One hundred and eighty-three elements were selected, which were either up- or down-regulated more than 2-fold at one or more time points after SISPH. Cluster analysis and generalization analysis showed that there were five distinct temporal patterns of gene expression. Eighty-six genes were unreported, associated with liver regeneration (LR).
CONCLUSION: Microarray analysis shows that the down regulated genes are much more than the up-regulated ones in SISPH; the numbers of genes expressed consistently are fewer than that expressed immediately; the genes expressed in high abundance are much fewer than that increased 2-5-fold. The comparison of SISPH with partial hepatectomy (PH) shows that the expression trends of most genes in SISPH and in PH are similar, but the expression of 43 genes is specifically altered in SISPH.
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Affiliation(s)
- Cun-Shuan Xu
- College of Life Science, Henan Normal University, Xinxiang 453002, Henan Province, China.
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Abstract
During embryonic development, the liver emerges from the foregut as a thickening of the ventral endodermal epithelium. The embryonic liver then develops into a bud of cells that proliferates and differentiates to eventually form the largest gland of the body. Prior to birth, the primary function of the liver is hematopoietic, and the organ receives little innervation during early development. Postnatally, the role of the liver changes and many different nerve types modulate its function. Although the liver shares a common embryonic origin with other foregut derivatives, such as the gallbladder and the pancreas, the development of its innervation exhibits distinct characteristics. In this review, we summarize what is known about the development of the hepatic innervation, draw comparisons with the intrinsic innervation of the gastrointestinal tract and associated organs, and discuss the potential role of molecular signals in guiding the nerves that innervate the liver.
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Affiliation(s)
- Jean-Marie Delalande
- Neural Development Unit, Institute of Child Health, University College London, UK
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Christoffels VM, Sassi H, Ruijter JM, Moorman AF, Grange T, Lamers WH. A mechanistic model for the development and maintenance of portocentral gradients in gene expression in the liver. Hepatology 1999; 29:1180-92. [PMID: 10094963 DOI: 10.1002/hep.510290413] [Citation(s) in RCA: 30] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/25/2023]
Abstract
In the liver, genes are expressed along a portocentral gradient. Based on their adaptive behavior, a gradient versus compartment type, and a dynamic versus stable type of gradient have been recognized. To understand at least in principle the development and maintenance of these gradients in gene expression in relation to the limited number of signal gradients, we propose a simple and testable model. The model uses portocentral gradients of signal molecules as input, while the output depends on two gene-specific variables, viz., the affinity of the gene for its regulatory factors and the degree of cooperativity that determines the response in the signal-transduction pathways. As a preliminary validity test for its performance, the model was tested on control and hormonally induced expression patterns of phosphoenolpyruvate carboxykinase (PCK), carbamoylphosphate synthetase I (CPS), and glutamine synthetase (GS). Affinity was found to determine the overall steepness of the gradient, whereas cooperativity causes these gradients to steepen locally, as is necessary for a compartment-like expression pattern. Interaction between two or more different signal gradients is necessary to ensure a stable expression pattern under different conditions. The diversity in sequence and arrangement of related DNA-response elements of genes appears to account for the gene-specific shape of the portocentral gradients in expression. The feasibility of testing the function of hepatocyte-specific DNA-response units in vivo is demonstrated by integrating such units into a ubiquitously active promoter/enhancer and analyzing the pattern of expression of these constructs in transgenic mice.
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Affiliation(s)
- V M Christoffels
- Department of Anatomy and Embryology, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands
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Abstract
Hepatic neuropeptide Y (NPY) innervation was studied by immunohistochemistry in various mature vertebrates including the eel, carp, bullfrog, turtle, chicken, mouse, rat, guinea pig, dog, monkey, and human. In addition, an ontogenetic study on hepatic NPY was made in developing mice and guinea pigs. In all species examined except the eel, NPY-like immunoreactivity was detected in nerve fibers. In the carp, bullfrog, turtle, chicken, mouse, and rat, NPY-positive fibers were distributed around the wall of hepatic vessels and the bile duct of the Glisson's sheath. The density of NPY-positive fibers increased with evolution. However, in the guinea pig, dog, monkey, and human, numerous NPY-positive fibers were observed not only in the Glisson's sheath but also in the liver parenchyma. Positive fibers formed a dense network that surrounded the hepatocytes. The present immunoelectron microscopic study has confirmed that NPY-positive terminals are closely apposed to hepatocytes. Ontogenically, NPY-positive fibers were first found in the embryonic liver of 19-day-old mice. Positive fibers increased with age, and the highest peak was seen 1 week after birth. However, NPY-positive nerve fibers were present abundantly in Glisson's sheath and in the hepatic parenchyma of neonatal (3 and 7 days old) guinea pigs in a distribution similar to that in mature animals. This ontogenetic pattern suggests that NPY plays a certain role in the developing liver.
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Affiliation(s)
- W G Ding
- Department of Physiology, Shiga University of Medical Science, Otsu, Japan
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Abstract
In the liver of humans, guinea pigs, cats, and tupaia, nerve endings are distributed all over the hepatic lobules from the portal spaces to the centralobular spaces. Nerve endings in the intralobular spaces are located mainly in the space of Disse, and are closely related to lipocytes. In the human liver, various neurotransmitters such as substance P (SP) exist in the nerve endings. Lipocytes are believed to contract through these substances. In fact, the contraction of lipocytes is induced by SP. Moreover, lipocytes possess endothelin (ET) receptors (ETA, ETB), and the cells are contracted by ET-1 by way of ET receptors in the autocrine or paracrine mechanism. Contraction of lipocytes seems to be related to the enhancement of the intracellular Ca2+ and inositol phosphates. In addition, alpha-smooth muscle actin, which is a contractile protein, exists in the cytoplasm of lipocytes. Lipocyte contractility may be similar to that of vascular smooth muscle cells. On the other hand, prostaglandin E2, Iloprost, and adrenomedullin cause the elevation of c-AMP levels in lipocytes and relax the cells. In addition, lipocytes produce nitric oxide (NO) and inhibit contractility by an autocrine mechanism related to NO. In this way, lipocytes appear to be associated with the regulation of hepatic sinusoidal microcirculation by contraction and relaxation. In the cirrhotic liver, intralobular innervation is decreased or absent, but ET-1 and NO are overexpressed. These phenomena indicate that lipocytes may play an important role in the sinusoidal microcirculation through these agents rather than through intralobular innervation in liver cirrhosis.
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Affiliation(s)
- T Ueno
- Second Department of Medicine, Kurume University School of Medicine, Japan
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Fukuda Y, Imoto M, Koyama Y, Miyazawa Y, Hayakawa T. Demonstration of noradrenaline-immunoreactive nerve fibres in the liver. J Int Med Res 1996; 24:466-72. [PMID: 8959530 DOI: 10.1177/030006059602400603] [Citation(s) in RCA: 22] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/03/2023] Open
Abstract
To demonstrate noradrenaline-immunoreactive nerve fibres in liver tissues, we used an antibody to noradrenaline in the immunostaining of liver tissues from rats, guinea-pigs and humans. The tissue specimens were fixed by perfusion or immersion with cacodylate buffer containing sodium metabisulphate and glutaraldehyde, and cryostat sections were prepared. An indirect peroxidase-labelled antibody method was used for staining noradrenaline. Noradrenaline-immunoreactive nerve fibres were localized around blood vessels in the portal area and around the central vein. There were differences between the species in the intralobular distribution of noradrenaline-immunoreactive fibres. Normal guinea-pig and human liver showed intralobular noradrenaline-immunoreactive fibres while rat liver did not. Noradrenaline-immunoreactive fibres were absent from regenerating nodules in a human cirrhotic liver. This method of demonstrating noradrenaline directly using perfusion- or immersion-fixation is appropriate for studying innervation in normal and damaged livers of various species including humans.
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Affiliation(s)
- Y Fukuda
- Second Department of Internal Medicine, Nagoya University School of Medicine, Japan
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Abstract
Although it has been known for many years that the liver receives a nerve supply, it is only with the advent of immunohistochemistry that this innervation has been analysed in depth. It is now appreciated not only that many different nerve types are present, but also that there are significant differences between species, especially in the degree of parenchymal innervation. This has stimulated more detailed investigation of the innervation of the human liver in both health and disease. At the same time, functional studies have been underlining the important roles that these nerves play in processes as diverse as osmoreception and liver regeneration. This article briefly reviews current understanding of the morphology and functions of the hepatic nerve supply.
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Affiliation(s)
- D G Tiniakos
- Department of Pathology, University of Patras, Greece
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