title: Inhibition of Janus kinase-2 signalling pathway ameliorates portal hypertensive syndrome in partial portal hypertensive and liver cirrhosis rats.
abstract: OBJECTIVE
  JAK2/STAT3 signalling promotes fibrosis, angiogenesis and inflammation in many diseases; however, the role of this pathway in portal hypertension remains obscure. This study aimed to explore the function of JAK2/STAT3 signalling in portal hypertension and estimate the potential therapeutic effect of treatment with the specific inhibitor AG490.
  
  
  METHODS
  Rats induced by partial portal vein ligation and common bile duct ligation were treated with AG490 for two weeks. Haemodynamic parameters were assessed. The levels of phospho-STAT3 protein and related cytokines were detected by western blotting of splanchnic organs. Liver, spleen and intestine characterization was performed using histological analyses. Peripheral blood cell counts were also detected.
  
  
  RESULTS
  High levels of phospho-STAT3 protein were detected in portal hypertensive rats. AG490 effectively inhibited JAK2/STAT3 signalling and its downstream cytokines and provided protective effects by decreasing splanchnic neovascularization and inflammation and by attenuating portal pressure and hyperdynamic splanchnic circulation. In cirrhosis rats, AG490 inhibited intrahepatic fibrosis, angiogenesis and inflammation. AG490 improved the peripheral blood cell counts and the splenomegaly observed in these rats.
  
  
  CONCLUSIONS
  JAK2/STAT3 signalling is essential in portal hypertension, and targeting JAK2/STAT3 may be a promising therapy to treat this condition.
authors: Department of General Surgery, TangDu Hospital, Fourth Military Medical University, Xi'an, China.
authors: Dong
authors: D
authors: Wang
authors: Department of General Surgery, TangDu Hospital, Fourth Military Medical University, Xi'an, China.
authors: Jikai
authors: J
authors: Yin
authors: Department of General Surgery, TangDu Hospital, Fourth Military Medical University, Xi'an, China.
authors: Rui
authors: R
authors: Dong
authors: Department of Orthopedics, TangDu Hospital, Fourth Military Medical University, Xi'an, China.
authors: Jian
authors: J
authors: Zhao
authors: Department of General Surgery, TangDu Hospital, Fourth Military Medical University, Xi'an, China.
authors: Qing
authors: Q
authors: Wang
authors: Department of General Surgery, TangDu Hospital, Fourth Military Medical University, Xi'an, China.
authors: Nan
authors: N
authors: Wang
authors: Laboratory of General Surgery Department, TangDu Hospital, Fourth Military Medical University, Xi'an, China.
authors: Shouli
authors: S
authors: Wang
authors: Department of General Surgery, TangDu Hospital, Fourth Military Medical University, Xi'an, China. Electronic address: dxlin0705@163.com.
authors: Xilin
authors: X
authors: Du
authors: Department of General Surgery, TangDu Hospital, Fourth Military Medical University, Xi'an, China. Electronic address: lujguo1963@163.com.
authors: Jianguo
authors: J
authors: Lu
mesh_terms: D000818:Animals; D015153:Blotting, Western; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004797:Enzyme-Linked Immunosorbent Assay; D006975:Hypertension, Portal / Q000188:drug therapy / Q000201:enzymology* / Q000503:physiopathology; D007150:Immunohistochemistry; D053614:Janus Kinase 2 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D008106:Liver Cirrhosis, Experimental / Q000188:drug therapy / Q000201:enzymology* / Q000503:physiopathology; D008297:Male; D017082:Portal Pressure; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects; D013577:Syndrome; D020032:Tyrphostins / Q000494:pharmacology*
chemical_list: D004791:Enzyme Inhibitors; D020032:Tyrphostins; C095512:alpha-cyano-(3,4-dihydroxy)-N-benzylcinnamide; C507927:Jak2 protein, rat; D053614:Janus Kinase 2
keywords: AG490; Cirrhosis; JAK2/STAT3 signalling; Portal hypertension