Literature DB >> 22594838

Endothelin-1 derived from spleen-activated Rho-kinase pathway in rats with secondary biliary cirrhosis.

Hideo Uehara1, Tomohiko Akahoshi, Hirohumi Kawanaka, Naotaka Hashimoto, Yoshihiro Nagao, Morimasa Tomikawa, Akinobu Taketomi, Ken Shirabe, Makoto Hashizume, Yoshihiko Maehara.   

Abstract

AIM: Splenectomy or partial splenic embolism has been reported to improve liver function in patients with hypersplenism and liver dysfunction. The aim of this study was to investigate the mechanism of improvement after splenectomy.
METHODS: Liver cirrhosis was induced by bile duct ligation (BDL). Rats underwent sham operation, splenectomy (Sp group), BDL, or BDL plus splenectomy (BDL + Sp group), and were subjected to experiments at 2 weeks after the operation. Portal venous pressure (PVP) and hepatic tissue blood flow (HTBF) were measured in each group. The plasma concentration of endothelin-1 (ET-1) and endothelial nitric oxide synthase (eNOS), RhoA and Rho-kinase expressions were studied.
RESULTS: There were significant differences in PVP (17.9 ± 0.91 vs 23.3 ± 3.91 cmH(2) O; P < 0.01) and HTBF (16.6 ± 1.72 vs 13.3 ± 1.82 mL/min; P < 0.01) between the BDL + Sp and BDL groups. In the liver of BDL rats, eNOS phosphorylation and NOx levels were decreased, accompanied by RhoA activation compared with the BDL + Sp group. Splenectomy decreased serum ET-1 levels, RhoA activation and consequently increased eNOS phosphorylation.
CONCLUSION: ET-1 derived from the spleen might increase intrahepatic resistance by downregulating Rho signaling in liver cirrhosis. Splenectomy for splenomegaly in liver cirrhosis might partially improve liver function by enhancing intrahepatic microcirculation.
© 2012 The Japan Society of Hepatology.

Entities:  

Year:  2012        PMID: 22594838     DOI: 10.1111/j.1872-034X.2012.01021.x

Source DB:  PubMed          Journal:  Hepatol Res        ISSN: 1386-6346            Impact factor:   4.288


  4 in total

Review 1.  Conceptual changes in small-for-size graft and small-for-size syndrome in living donor liver transplantation.

Authors:  Toru Ikegami; Jong Man Kim; Dong-Hwan Jung; Yuji Soejima; Dong-Sik Kim; Jae-Won Joh; Sung-Gyu Lee; Tomoharu Yoshizumi; Masaki Mori
Journal:  Korean J Transplant       Date:  2019-12-31

2.  Spleen Regulates Hematopoietic Stem/Progenitor Cell Functions Through Regulation of EGF in Cirrhotic Hypersplenism.

Authors:  Peijun Wang; Zhenzhen Li; Song Ren; Jiangwei Li; Jun Yang; Guangyao Kong; An Jiang; Zongfang Li
Journal:  Dig Dis Sci       Date:  2018-05-03       Impact factor: 3.199

3.  Endothelin receptors promote schistosomiasis-induced hepatic fibrosis via splenic B cells.

Authors:  Hongyan Kong; Jinan He; Shusen Guo; Qiqin Song; Dandan Xiang; Ran Tao; Haijing Yu; Guang Chen; Zhiyong Huang; Qin Ning; Jiaquan Huang
Journal:  PLoS Pathog       Date:  2020-10-19       Impact factor: 6.823

4.  Sodium ferulate lowers portal pressure in rats with secondary biliary cirrhosis through the RhoA/Rho-kinase signaling pathway: a preliminary study.

Authors:  Lai Wei; Juan Yang; Min Wang; Sheng-Nan Xu; Hua-Min Liang; Qi Zhou
Journal:  Int J Mol Med       Date:  2014-08-19       Impact factor: 4.101

  4 in total

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