title: Intrahepatic upregulation of MRTF-A signaling contributes to increased hepatic vascular resistance in cirrhotic rats with portal hypertension.
abstract: BACKGROUND
  Portal hypertension in cirrhosis is mediated, in part, by increased intrahepatic resistance, reflecting massive structural changes associated with fibrosis and intrahepatic vasoconstriction. Activation of the Rho/MRTF/SRF signaling pathway is essential for the cellular regulatory network of fibrogenesis. The aim of this study was to investigate MRTF-A-mediated regulation of intrahepatic fibrogenesis in cirrhotic rats.
  
  
  METHODS
  Portal hypertension was induced in rats via an injection of CCl4oil. Hemodynamic measurements were obtained using a polyethylene PE-50 catheter and pressure transducers. Expression of hepatic fibrogenesis was measured using histological staining. Expression of protein was measured using western blotting.
  
  
  RESULTS
  Upregulation of MRTF-A protein expression in the livers of rats with CCl4-induced cirrhosis was relevant to intrahepatic resistance and hepatic fibrogenesis in portal hypertensive rats with increased modeling time. Inhibition of MRTF-A by CCG-1423 decelerated hepatic fibrosis, decreased intrahepatic resistance and portal pressure, and alleviated portal hypertension.
  
  
  CONCLUSIONS
  Increased intrahepatic resistance in rats with CCl4-induced portal hypertension is associated with an upregulation of MRTF-A signaling. Inhibition of this pathway in the liver can decrease hepatic fibrosis and intrahepatic resistance, as well as reduce portal pressure in cirrhotic rats with CCl4-induced portal hypertension.
authors.affiliation: Department of General Surgery, Ninth People's Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai 201999, PR China.
authors.forename: Lei
authors.initials: L
authors.lastname: Zheng
authors.affiliation: Department of Gastrointestinal Surgery, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai 200127, PR China.
authors.forename: Jun
authors.initials: J
authors.lastname: Qin
authors.affiliation: Department of Gastrointestinal Surgery, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai 200127, PR China.
authors.forename: Longci
authors.initials: L
authors.lastname: Sun
authors.affiliation: Department of General Surgery, Ninth People's Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai 201999, PR China.
authors.forename: Liang
authors.initials: L
authors.lastname: Gui
authors.affiliation: Department of General Surgery, Ninth People's Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai 201999, PR China.
authors.forename: Chihao
authors.initials: C
authors.lastname: Zhang
authors.affiliation: Department of General Surgery, Ninth People's Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai 201999, PR China.
authors.forename: Yijun
authors.initials: Y
authors.lastname: Huang
authors.affiliation: Department of General Surgery, Ninth People's Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai 201999, PR China.
authors.forename: Wensheng
authors.initials: W
authors.lastname: Deng
authors.affiliation: Department of Physiology, New York Medical College, Valhalla, New York 10595, USA.
authors.forename: An
authors.initials: A
authors.lastname: Huang
authors.affiliation: Department of Physiology, New York Medical College, Valhalla, New York 10595, USA.
authors.forename: Dong
authors.initials: D
authors.lastname: Sun
authors.affiliation: Department of General Surgery, Ninth People's Hospital, School of Medicine, Shanghai Jiaotong University, No. 639, Zhizaoju Road, Huangpu District, Shanghai 200011, PR China. Electronic address: luotysy@sina.com.
authors.forename: Meng
authors.initials: M
authors.lastname: Luo
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D006975:Hypertension, Portal / Q000209:etiology; D008106:Liver Cirrhosis, Experimental / Q000150:complications / Q000378:metabolism* / Q000473:pathology; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction; D014157:Transcription Factors / Q000378:metabolism*; D015854:Up-Regulation; D014655:Vascular Resistance
chemical_list: D015415:Biomarkers; D014157:Transcription Factors; C557977:myocardin-related transcription factor-A, rat