Basic Study
Copyright ©The Author(s) 2018. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Aug 7, 2018; 24(29): 3273-3280
Published online Aug 7, 2018. doi: 10.3748/wjg.v24.i29.3273
High expression of type I inositol 1,4,5-trisphosphate receptor in the kidney of rats with hepatorenal syndrome
Jing-Bo Wang, Ye Gu, Ming-Xiang Zhang, Shun Yang, Yan Wang, Wei Wang, Xi-Ran Li, Yi-Tong Zhao, Hai-Tao Wang
Jing-Bo Wang, Ye Gu, Ming-Xiang Zhang, Yan Wang, Wei Wang, Xi-Ran Li, Yi-Tong Zhao, Liver Cirrhosis Ward, the Sixth People’s Hospital of Shenyang, Shenyang 110006, Liaoning Province, China
Shun Yang, Liaoning Cancer Hospital & Institute, Shenyang 110042, Liaoning Province, China
Hai-Tao Wang, Department of General Surgery, the Second Affiliated Hospital of Shenyang Medical College, Shenyang 110002, Liaoning Province, China
Author contributions: Wang JB, Wang HT and Gu Y contributed equally to this work, and all of them were involved in the design and performing of the experiment, data analysis and drafting of the article; Zhang MX, Wang Y and Yang S participated in the study, hepatic and renal pathological examination and biochemical test; Li XR, Wang W and Zhao YT completed data analysis, Western blot analysis and real-time PCR and drafting of the paper.
Supported by Natural Science Foundation of Liaoning Province, No. 20170540826; Science and Technology Program of Shenyang City, No. 18-014-4-49; and Innovation Support Program of Shenyang City for Young and Middle-Aged Researchers, No. RC170051.
Institutional animal care and use committee statement: This study was approved by the Ethical Committee of the Sixth People’s Hospital of Shenyang.
Conflict-of-interest statement: The authors declare no conflicts of interest.
Data sharing statement: No additional data are available.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Hai-Tao Wang, MSc, Surgeon, Department of General Surgery, the Second Affiliated Hospital of Shenyang Medical College, No. 20, Beijiuma Road, Heping District, Shenyang 110002, Liaoning Province, China. whtszyypwk@163.com
Telephone: +86-18002452018 Fax: +86-24-31251510
Received: May 3, 2018
Peer-review started: May 4, 2018
First decision: June 6, 2018
Revised: June 19, 2018
Accepted: June 27, 2018
Article in press: June 27, 2018
Published online: August 7, 2018
Processing time: 92 Days and 8.7 Hours
ARTICLE HIGHLIGHTS
Research background

Hepatorenal syndrome (HRS) is one of the common and severe complications of liver failure and advanced liver disease, with approximately 55% of these patients developing this severe complication. At present, HRS has unclear pathogenesis, limited treatment options, and poor therapeutic efficacy. Once renal dysfunction aggravates rapidly, 60%-80% of patients with HRS will die. Therefore, elucidating the mechanism underlying the development and progression of HRS and taking effective preventive and therapeutic measures may improve the success rate of rescue, the incidence rate, and the mortality rate of HRS.

Research motivation

To detect the protein and mRNA expression of type I inositol 1,4,5-trisphosphate receptor (IP3RI) in the kidney of rats with HRS by Western blot and real-time PCR.

Research objectives

To explore whether high expression of renal IP3RI is associated with Ca2+ influx in vascular smooth muscle cells of glomerular afferent arteries and glomerular mesangial cells in rats with HRS.

Research methods

D-galactosamine (D-GalN) and/or lipopolysaccharide (LPS) were used to treat male Sprague-Dawley (SD) rats via the tail vein. Twelve hours after injection, massive hepatocyte necrosis with severe hemorrhage occurred in the liver, while renal tissue had a normal morphology. In addition, liver and kidney function was impaired severely, and serum biochemical indexes exhibited significant changes. These changes were consistent with the clinical features of HRS. Western blot and real-time PCR were then used to detect the protein and mRNA expression of renal IP3RI, respectively.

Research results

IP3RI protein expression was significantly elevated in rats with HRS. The elevation began at 3 h and reached the peak at 12 h. IP3RI mRNA expression was also significantly elevated in rats with HRS. The elevation began at 3 h and peaked at 9 h.

Research conclusions

Joint D-GalN/LPS administration can induce HRS in SD rats at 12 h, which is concomitant with peaked IP3RI protein and mRNA expression in the kidney. Increased expression of IP3RI may be closely associated with HRS development and progression.

Research perspectives

Our results suggest that IP3RI may be a signal molecule involved in the reduction of renal blood flow induced by renal vasoconstriction in HRS, thus providing a theoretical basis for further research of the pathogenesis of HRS. Gene silencing technology may be adopted to further elucidate the role of IP3RI in the pathogenesis of HRS.