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Shen YZ, Yang GP, Ma QM, Wang YS, Wang X. Regulation of lncRNA-ENST on Myc-mediated mitochondrial apoptosis in mesenchymal stem cells: In vitro evidence implicated for acute lung injury therapeutic potential. World J Stem Cells 2025; 17:100079. [DOI: 10.4252/wjsc.v17.i3.100079] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/06/2024] [Revised: 12/04/2024] [Accepted: 02/05/2025] [Indexed: 03/21/2025] Open
Abstract
BACKGROUND Acute lung injury (ALI) is a fatal and heterogeneous disease. While bone marrow mesenchymal stem cells (BMSCs) have shown promise in ALI repair, their efficacy is compromised by a high apoptotic percentage. Preliminary findings have indicated that long noncoding RNA (lncRNA)-ENST expression is markedly downregulated in MSCs under ischemic and hypoxic conditions, establishing a rationale for in vitro exploration.
AIM To elucidate the role of lncRNA-ENST00000517482 (lncRNA-ENST) in modulating MSC apoptosis.
METHODS Founded on ALI in BEAS-2B cells with lipopolysaccharide, this study employed a transwell co-culture system to study BMSC tropism. BMSCs were genetically modified to overexpress or knockdown lncRNA-ENST. After analyzing the effects on autophagy, apoptosis and cell viability, the lncRNA-ENST/miR-539/c-MYC interaction was confirmed by dual-luciferase assays.
RESULTS These findings have revealed a strong correlation between lncRNA-ENST levels and the apoptotic and autophagic status of BMSCs. On the one hand, the over-expression of lncRNA-ENST, as determined by Cell Counting Kit-8 assays, increased the expression of autophagy markers LC3B, ATG7, and ATG5. On the other hand, it reduced apoptosis and boosted BMSC viability. In co-cultures with BEAS-2B cells, lncRNA-ENST overexpression also improved cell vitality. Additionally, by downregulating miR-539 and upregulating c-MYC, lncRNA-ENST was found to influence mitochondrial membrane potential, enhance BMSC autophagy, mitigate apoptosis and lower the secretion of pro-inflammatory cytokines interleukin-6 and interleukin-1β. Collectively, within the in vitro framework, these results have highlighted the therapeutic potential of BMSCs in ALI and the pivotal regulatory role of lncRNA-ENST in miR-539 and apoptosis in lipopolysaccharide-stimulated BEAS-2B cells.
CONCLUSION Our in vitro results show that enhanced lncRNA ENST expression can promote BMSC proliferation and viability by modulating the miR-539/c-MYC axis, reduce apoptosis and induce autophagy, which has suggested its therapeutic potential in the treatment of ALI.
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Affiliation(s)
- Ye-Zhou Shen
- Department of Critical Care Medicine, Shanghai East Hospital, Tongji University, Shanghai 200120, China
| | - Guang-Ping Yang
- Medical Center of Burn Plastic and Wound Repair, The First Affiliated Hospital of Nanchang University, Nanchang 330006, Jiangxi Province, China
| | - Qi-Min Ma
- Department of Critical Care Medicine, Shanghai East Hospital, Tongji University, Shanghai 200120, China
| | - Yu-Song Wang
- Department of Critical Care Medicine, Shanghai East Hospital, Tongji University, Shanghai 200120, China
| | - Xin Wang
- Medical Center of Burn Plastic and Wound Repair, The First Affiliated Hospital of Nanchang University, Nanchang 330006, Jiangxi Province, China
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Yin C, Wang X, Tao Y, Wu X, Li Y, Li H, Liang Y. Notch 2 from bone marrow mesenchymal stem cells alleviates smoke inhalation-induced lung injury by mediating alveolar cell differentiation. J Mol Histol 2025; 56:113. [PMID: 40119225 DOI: 10.1007/s10735-025-10393-8] [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: 04/19/2024] [Accepted: 03/06/2025] [Indexed: 03/24/2025]
Abstract
BACKGROUND Smoke inhalation-induced lung injury (SILI) is the major fatality in fire- and blast-related accidents. Bone marrow mesenchymal stem cells (BMSCs) have a potential therapeutic role in SILI through directional differentiation into AT1, AT2, and pulmonary vascular endothelial cells. The present study proposes to evaluate the effect of Notch 2 on the directional differentiation of BMSCs and to characterize its reparative role in a SILI model. METHODS pGMLV-SC5 RNAi and pcDNA 3.1 lentivirus exogenously regulate Notch 2 expression in rat-derived BMSCs and BMSCs were injected into the tail vein of the SILI rat model. H&E, Masson and TUNEL stains characterized pathological changes in rat lung tissue. ELISA, western blot, and RT-qPCR identified inflammatory factors (IL-1β, IL-6 and TNF-α), Notch 2 pathway- (Notch 2 and Hes1), lung fibrosis- (α-SMA and E-cadherin), AT1- (AQP5), and AT2- (SPC and SPD) associated markers. RESULTS pGMLV-SC5 RNAi or pcDNA 3.1 lentivirus could decrease or increase Notch 2 expression in BMSCs. In vivo imaging showed that BMSCs could be localized in the lungs of the SILI model at 24 h after model development. Treatment with BMSCs alleviated diffuse congestion, lung fibrosis, and alveolar cell apoptosis in lung tissues of the SILI model. Treatment of BMSCs decreased the levels of IL-1β, IL-6, TNF-α, and α-SMA and increased the expression of Notch 2, Hes1, E-cadherin, AQP5, SPC, and SPD in the SILI model. Overexpression of Notch 2 enhances the therapeutic effect of BMSCs on lung injury in the SILI model. Notably, overexpression of Notch 2 attenuated the BMSCs-induced upregulation of AQP5 expression and enhanced the BMSCs-induced upregulation of SPC and SPD expression. CONCLUSION Notch 2 contributes to lung injury repair in the SILI rat model by facilitating the differentiation of BMSCs to AT2. This study provides a new idea and target for the treatment of BMSCs for SILI.
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Affiliation(s)
- Cunping Yin
- Department of Vascular Surgery Department, 920th Hospital of PLA Joint Logistics Support Force, 212 Daguan Road, Kunming, Yunnan, China
| | - Xiaoyan Wang
- Department of Neurology, 920th Hospital of PLA Joint Logistics Support Force, 212 Daguan Road, Kunming, Yunnan, China
| | - Yanmei Tao
- Department of Geriatric, 920th Hospital of PLA Joint Logistics Support Force, 212 Daguan Road, Kunming, Yunnan, China
- Kunming Medical University, No. 1168 Chunrong West Road, Yuhua Street, Kunming, Yunnan, China
| | - Xiaoqing Wu
- Department of Emergency, 920th Hospital of PLA Joint Logistics Support Force, 212 Daguan Road, Kunming, Yunnan, China
| | - Yuan Li
- Department of Geriatric, 920th Hospital of PLA Joint Logistics Support Force, 212 Daguan Road, Kunming, Yunnan, China
| | - Haiping Li
- Department of Geriatric, 920th Hospital of PLA Joint Logistics Support Force, 212 Daguan Road, Kunming, Yunnan, China
| | - Yuan Liang
- Department of Geriatric, 920th Hospital of PLA Joint Logistics Support Force, 212 Daguan Road, Kunming, Yunnan, China.
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Huang S, Li Y, Zeng J, Chang N, Cheng Y, Zhen X, Zhong D, Chen R, Ma G, Wang Y. Mesenchymal Stem/Stromal Cells in Asthma Therapy: Mechanisms and Strategies for Enhancement. Cell Transplant 2023; 32:9636897231180128. [PMID: 37318186 DOI: 10.1177/09636897231180128] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 06/16/2023] Open
Abstract
Asthma is a complex and heterogeneous disease characterized by chronic airway inflammation, airway hyperresponsiveness, and airway remodeling. Most asthmatic patients are well-established using standard treatment strategies and advanced biologicals. However, a small group of patients who do not respond to biological treatments or are not effectively controlled by available treatment strategies remain a clinical challenge. Therefore, new therapies are urgently needed for poorly controlled asthma. Mesenchymal stem/stromal cells (MSCs) have shown therapeutic potential in relieving airway inflammation and repairing impaired immune balance in preclinical trials owing to their immunomodulatory abilities. Noteworthy, MSCs exerted a therapeutic effect on steroid-resistant asthma with rare side effects in asthmatic models. Nevertheless, adverse factors such as limited obtained number, nutrient and oxygen deprivation in vitro, and cell senescence or apoptosis affected the survival rate and homing efficiency of MSCs, thus limiting the efficacy of MSCs in asthma. In this review, we elaborate on the roles and underlying mechanisms of MSCs in the treatment of asthma from the perspective of their source, immunogenicity, homing, differentiation, and immunomodulatory capacity and summarize strategies to improve their therapeutic effect.
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Affiliation(s)
- Si Huang
- Department of Pediatrics, Shunde Women and Children's Hospital of Guangdong Medical University, Foshan, China
- Institute of Respiratory Diseases, Shunde Women and Children's Hospital, Guangdong Medical University, Foshan, China
| | - Yiyang Li
- Department of Pediatrics, The Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, China
| | - Jieqing Zeng
- Department of Pediatrics, Shunde Women and Children's Hospital of Guangdong Medical University, Foshan, China
- Institute of Respiratory Diseases, Shunde Women and Children's Hospital, Guangdong Medical University, Foshan, China
| | - Ning Chang
- Department of Pediatrics, Shunde Women and Children's Hospital of Guangdong Medical University, Foshan, China
- Institute of Respiratory Diseases, Shunde Women and Children's Hospital, Guangdong Medical University, Foshan, China
| | - Yisen Cheng
- Department of Pediatrics, Shunde Women and Children's Hospital of Guangdong Medical University, Foshan, China
- Institute of Respiratory Diseases, Shunde Women and Children's Hospital, Guangdong Medical University, Foshan, China
| | - Xiangfan Zhen
- Department of Pediatrics, Shunde Women and Children's Hospital of Guangdong Medical University, Foshan, China
- Institute of Respiratory Diseases, Shunde Women and Children's Hospital, Guangdong Medical University, Foshan, China
| | - Dan Zhong
- Department of Pediatrics, Shunde Women and Children's Hospital of Guangdong Medical University, Foshan, China
- Institute of Respiratory Diseases, Shunde Women and Children's Hospital, Guangdong Medical University, Foshan, China
| | - Riling Chen
- Department of Pediatrics, Shunde Women and Children's Hospital of Guangdong Medical University, Foshan, China
- Institute of Respiratory Diseases, Shunde Women and Children's Hospital, Guangdong Medical University, Foshan, China
| | - Guoda Ma
- Department of Pediatrics, Shunde Women and Children's Hospital of Guangdong Medical University, Foshan, China
- Institute of Respiratory Diseases, Shunde Women and Children's Hospital, Guangdong Medical University, Foshan, China
| | - Yajun Wang
- Department of Pediatrics, Shunde Women and Children's Hospital of Guangdong Medical University, Foshan, China
- Institute of Respiratory Diseases, Shunde Women and Children's Hospital, Guangdong Medical University, Foshan, China
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Liu C, Xiao K, Xie L. Advances in mesenchymal stromal cell therapy for acute lung injury/acute respiratory distress syndrome. Front Cell Dev Biol 2022; 10:951764. [PMID: 36036014 PMCID: PMC9399751 DOI: 10.3389/fcell.2022.951764] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/24/2022] [Accepted: 07/19/2022] [Indexed: 11/29/2022] Open
Abstract
Acute lung injury (ALI)/acute respiratory distress syndrome (ARDS) develops rapidly and has high mortality. ALI/ARDS is mainly manifested as acute or progressive hypoxic respiratory failure. At present, there is no effective clinical intervention for the treatment of ALI/ARDS. Mesenchymal stromal cells (MSCs) show promise for ALI/ARDS treatment due to their biological characteristics, easy cultivation, low immunogenicity, and abundant sources. The therapeutic mechanisms of MSCs in diseases are related to their homing capability, multidirectional differentiation, anti-inflammatory effect, paracrine signaling, macrophage polarization, the polarization of the MSCs themselves, and MSCs-derived exosomes. In this review, we discuss the pathogenesis of ALI/ARDS along with the biological characteristics and mechanisms of MSCs in the treatment of ALI/ARDS.
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Affiliation(s)
- Chang Liu
- School of Medicine, Nankai University, Tianjin, China
- Center of Pulmonary and Critical Care Medicine, Chinese People’s Liberation Army (PLA) General Hospital, Beijing, China
- Medical School of Chinese People’s Liberation Army (PLA), Beijing, China
| | - Kun Xiao
- Center of Pulmonary and Critical Care Medicine, Chinese People’s Liberation Army (PLA) General Hospital, Beijing, China
- Medical School of Chinese People’s Liberation Army (PLA), Beijing, China
- *Correspondence: Kun Xiao, ; Lixin Xie,
| | - Lixin Xie
- School of Medicine, Nankai University, Tianjin, China
- Center of Pulmonary and Critical Care Medicine, Chinese People’s Liberation Army (PLA) General Hospital, Beijing, China
- Medical School of Chinese People’s Liberation Army (PLA), Beijing, China
- *Correspondence: Kun Xiao, ; Lixin Xie,
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Mercel AI, Gillis DC, Sun K, Dandurand BR, Weiss JM, Tsihlis ND, Maile R, Kibbe MR. A comparative study of a preclinical survival model of smoke inhalation injury in mice and rats. Am J Physiol Lung Cell Mol Physiol 2020; 319:L471-L480. [PMID: 32697601 DOI: 10.1152/ajplung.00241.2020] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022] Open
Abstract
Smoke inhalation injury increases morbidity and mortality. Clinically relevant animal models are necessary for the continued investigation of the pathophysiology of inhalation injury and the development of therapeutics. The goal of our research was threefold: 1) to develop a reproducible survival model of smoke inhalation injury in rats that closely resembled our previous mouse model, 2) to validate the rat smoke inhalation injury model using a variety of laboratory techniques, and 3) to compare and contrast our rat model with both the well-established mouse model and previously published rat models to highlight our improvements on smoke delivery and lung injury. Mice and rats were anesthetized, intubated, and placed in custom-built smoke chambers to passively inhale woodchip-generated smoke. Bronchoalveolar lavage fluid (BALF) and lung tissue were collected for confirmatory tests. Lung sections were hematoxylin and eosin stained, lung edema was assessed with wet-to-dry (W/D) ratio, and inflammatory cell infiltration and cytokine elevation were evaluated using flow cytometry, immunohistochemistry, and ELISA. We confirmed that our mouse and rat models of smoke inhalation injury mimic the injury seen after human burn inhalation injury with evidence of pulmonary edema, neutrophil infiltration, and inflammatory cytokine elevation. Interestingly, rats mounted a more severe immunological response compared with mice. In summary, we successfully validated a reliable and clinically translatable survival model of lung injury and immune response in rats and mice and characterized the extent of this injury. These animal models allow for the continued study of smoke inhalation pathophysiology to ultimately develop a better therapeutic.
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Affiliation(s)
- Alexandra I Mercel
- Department of Surgery, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina
| | - David C Gillis
- Department of Surgery, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina
| | - Kui Sun
- Department of Surgery, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina
| | - Brooke R Dandurand
- Department of Surgery, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina
| | - Jenna M Weiss
- Department of Surgery, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina
| | - Nick D Tsihlis
- Department of Surgery, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina
| | - Rob Maile
- Department of Surgery, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina.,Department of Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina.,Curriculum of Toxicology and Environmental Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina
| | - Melina R Kibbe
- Department of Surgery, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina.,Department of Biomedical Engineering, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina
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6
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BMSC-derived exosomes alleviate smoke inhalation lung injury through blockade of the HMGB1/NF-κB pathway. Life Sci 2020; 257:118042. [PMID: 32621926 DOI: 10.1016/j.lfs.2020.118042] [Citation(s) in RCA: 23] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/15/2020] [Revised: 06/21/2020] [Accepted: 06/29/2020] [Indexed: 12/12/2022]
Abstract
AIMS To investigate the role of bone marrow mesenchymal stem cell (BMSC)-derived exosomes in smoke inhalation lung injury. MAIN METHODS In this study, we initially isolated exosomes from BMSCs and identified them by western blot and transmission electron microscopy. BMSC-derived exosomes were then used to treat in vitro and in vivo models of smoke inhalation lung injury. Pathologic alterations in lung tissue, the levels of inflammatory factors and apoptosis-related factors, and the expression of HMGB1 and NF-κB were determined to evaluate the therapeutic effect of BMSC-derived exosomes. KEY FINDINGS We found that BMSC-derived exosomes could alleviate the injury caused by smoke inhalation. Smoke inhalation increased the levels of inflammatory factors and apoptosis-related factors and the expression of HMGB1 and NF-κB, and these increases were reversed by BMSC-derived exosomes. HMGB1 overexpression abrogated the exosome-induced decreases in inflammatory factors, apoptosis-related factors and NF-κB. SIGNIFICANCE Collectively, these results indicate that BMSC-derived exosomes can effectively alleviate smoke inhalation lung injury by inhibiting the HMGB1/NF-κB pathway, suggesting that exosome, a noncellular therapy, is a potential therapeutic strategy for inhalation lung injury.
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7
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Yang X, Zhou Z, Mao Z, Shen M, Chen N, Miao D. Role of p53 deficiency in socket healing after tooth extractions. J Mol Histol 2020; 51:55-65. [PMID: 32006186 DOI: 10.1007/s10735-020-09856-x] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/22/2019] [Accepted: 01/26/2020] [Indexed: 12/17/2022]
Abstract
p53 is known to advance the cell arrest and cell senescence in human tumors. In this study, we displayed that osteogenic ability of p53-knockout (p53-/-) mice was significantly increased in the tooth extraction socket compared with wild-type (WT) counterparts. Bone marrow mesenchymal stem cells (BM-MSCs) from mandibular were collected and exhibited with elevated proliferation potential and colony-forming units compared with the control, as well as stronger mineral deposits and osteogenic markers. Besides, the bone mass and bone parameter in p53-/- mice were markedly enhanced compared with the counterpart after extractions by micro-CT. Masson's trichrome staining and immunohistochemistry also revealed that new bone filling and osterix/osteocalcin (Osx/OCN)-immunopositive staining in p53-/- mice were remarkably increased at each time point. Furthermore, consistent with the enhanced osteogenic markers, the angiogenic marker of blood vessels (alpha smooth muscle actin, α-SMA) was significantly elevated in p53-/- mice in contrast to WT mice. Importantly, we found that the osteoclast numbers exhibited an increased trend in p53-/- mice compared with WT mice during socket healing. Collectively, our result suggest that p53 deficiency could promote the osteogenesis and angiogenesis in the tooth extraction socket and might lend possibility for p53-based therapeutic approaches in acceleration of extraction bone healing.
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Affiliation(s)
- Xiaohan Yang
- The Research Center for Bone and Stem Cells, Nanjing Medical University, Nanjing, China.,Jiangsu Key Laboratory of Oral Diseases, Nanjing Medical University, No. 140, Han Zhong Road, Nanjing, 210029, People's Republic of China.,Department of Stomatology, The Second Affiliated Hospital of Nanjing Medical University, No. 262, Zhong Shan North Road, Nanjing, 210003, People's Republic of China
| | - Zhixuan Zhou
- Department of Polyclinic, Affiliated Hospital of Stomatology, Nanjing Medical University, No. 136, Han Zhong Road, Nanjing, 210029, People's Republic of China
| | - Zhiyuan Mao
- The Research Center for Bone and Stem Cells, Nanjing Medical University, Nanjing, China.,Department of Stomatology, The Second Affiliated Hospital of Nanjing Medical University, No. 262, Zhong Shan North Road, Nanjing, 210003, People's Republic of China
| | - Ming Shen
- Department of Polyclinic, Affiliated Hospital of Stomatology, Nanjing Medical University, No. 136, Han Zhong Road, Nanjing, 210029, People's Republic of China
| | - Ning Chen
- Jiangsu Key Laboratory of Oral Diseases, Nanjing Medical University, No. 140, Han Zhong Road, Nanjing, 210029, People's Republic of China. .,Department of Dental Implant, Affiliated Hospital of Stomatology, Nanjing Medical University, No. 136, Han Zhong Road, Nanjing, 210029, People's Republic of China.
| | - Dengshun Miao
- The Research Center for Bone and Stem Cells, Nanjing Medical University, Nanjing, China. .,Department of Stomatology, The Second Affiliated Hospital of Nanjing Medical University, No. 262, Zhong Shan North Road, Nanjing, 210003, People's Republic of China.
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Nathan N, Sileo C, Thouvenin G, Berdah L, Delestrain C, Manali E, Papiris S, Léger PL, Pointe HDL, l'Hermine AC, Clement A. Pulmonary Fibrosis in Children. J Clin Med 2019; 8:E1312. [PMID: 31455000 PMCID: PMC6780823 DOI: 10.3390/jcm8091312] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/16/2019] [Revised: 08/14/2019] [Accepted: 08/21/2019] [Indexed: 12/20/2022] Open
Abstract
: Pulmonary fibrosis (PF) is a very rare condition in children, which may be observed in specific forms of interstitial lung disease. None of the clinical, radiological, or histological descriptions used for PF diagnosis in adult patients, especially in situations of idiopathic PF, can apply to pediatric situations. This observation supports the view that PF expression may differ with age and, most likely, may cover distinct entities. The present review aims at summarizing the current understanding of PF pathophysiology in children and identifying suitable diagnostic criteria.
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Affiliation(s)
- Nadia Nathan
- Pediatric Pulmonology Department, Reference Center for Rare Lung Diseases (RespiRare), Armand Trousseau Hospital, Assistance Publique Hôpitaux de Paris (AP-HP), 75012 Paris, France.
- Inserm UMR_S933, Sorbonne Université, 75012 Paris, France.
| | - Chiara Sileo
- Pediatric Radiology Department, Armand Trousseau Hospital, AP-HP, 75012 Paris, France
| | - Guillaume Thouvenin
- Pediatric Pulmonology Department, Reference Center for Rare Lung Diseases (RespiRare), Armand Trousseau Hospital, Assistance Publique Hôpitaux de Paris (AP-HP), 75012 Paris, France
| | - Laura Berdah
- Pediatric Pulmonology Department, Reference Center for Rare Lung Diseases (RespiRare), Armand Trousseau Hospital, Assistance Publique Hôpitaux de Paris (AP-HP), 75012 Paris, France
| | - Céline Delestrain
- Pediatric Pulmonology Department, Reference Center for Rare Lung Diseases (RespiRare), Armand Trousseau Hospital, Assistance Publique Hôpitaux de Paris (AP-HP), 75012 Paris, France
| | - Effrosyne Manali
- nd Pulmonary Medicine Department, General University Hospital "Attikon", Medical School, National and Kapodistrian University of Athens, 12462 Athens, Greece
| | - Spyros Papiris
- nd Pulmonary Medicine Department, General University Hospital "Attikon", Medical School, National and Kapodistrian University of Athens, 12462 Athens, Greece
| | - Pierre-Louis Léger
- Intensive Care Unit, Armand Trousseau Hospital, AP-HP, 75012 Paris, France
| | | | | | - Annick Clement
- Pediatric Pulmonology Department, Reference Center for Rare Lung Diseases (RespiRare), Armand Trousseau Hospital, Assistance Publique Hôpitaux de Paris (AP-HP), 75012 Paris, France
- Inserm UMR_S933, Sorbonne Université, 75012 Paris, France
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