Impairment of transforming growth factor beta signaling in caveolin-1-deficient hepatocytes: role in liver regeneration
Authors: Paloma Martín-Sanz
Rafael Mayoral
Lisardo Boscá
Ángela M Valverde
Águeda González-Rodríguez
Cristina Llorente Izquierdo
Journal: Journal of Biological Chemistry (2010)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: Caveolin-1; liver regeneration; TGF-beta signaling; hepatocytes; SnoN
Affiliations: From the Instituto de Investigaciones Biomédicas "Alberto Sols," Consejo Superior de Investigaciones Científicas, Arturo Duperier 4, 28029 Madrid; the Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas, Villarroel 170, 08036 Barcelona, and., From the Instituto de Investigaciones Biomédicas "Alberto Sols," Consejo Superior de Investigaciones Científicas, Arturo Duperier 4, 28029 Madrid; the Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas, Mallorca 183, 08036 Barcelona, Spain., From the Instituto de Investigaciones Biomédicas "Alberto Sols," Consejo Superior de Investigaciones Científicas, Arturo Duperier 4, 28029 Madrid., From the Instituto de Investigaciones Biomédicas "Alberto Sols," Consejo Superior de Investigaciones Científicas, Arturo Duperier 4, 28029 Madrid; the Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas, Villarroel 170, 08036 Barcelona, and. Electronic address: .

Abstract:  Caveolin-1 (Cav-1) is the main structural protein of caveolae and plays an important role in various cellular processes such as vesicular transport, cholesterol homeostasis, and signal transduction pathways. The expression and functional role of Cav-1 have been reported in liver and in hepatocyte cell lines, in human cirrhotic liver, and in hepatocellular carcinomas. Previous studies demonstrated that Cav-1 was dispensable for liver regeneration, because Cav-1(-/-) animals survived and fully regenerated liver function and size after partial hepatectomy. In this study, we have investigated the mechanisms by which the lack of Cav-1 accelerates liver regeneration after partial hepatectomy. The data show that transforming growth factor beta (TGF-beta) signaling is impaired in regenerating liver of Cav-1(-/-) mice and in hepatocytes derived from these animals. TGF-beta receptors I and II do not colocalize in the same membrane fraction in the hepatocytes derived from Cav-1(-/-) mice, as Smad2/3 signaling decreased in the absence of Cav-1 at the time that the transcriptional corepressor SnoN accumulates. Accordingly, the expression of TGF-beta target genes, such as plasminogen activator inhibitor-1, is decreased due to the presence of the high levels of SnoN. Moreover, hepatocyte growth factor inhibited TGF-beta signaling in the absence of Cav-1 by increasing SnoN expression. Taken together, these data might help to unravel why Cav-1-deficient mice exhibit an accelerated liver regeneration after partial hepatectomy and add new insights on the molecular mechanisms controlling the initial commitment to hepatocyte proliferation. 

Retracted: No

PubPeer comments:
 Figure 2C: More similar than expected (constrast enhanced). Could authors check please? ![file] , 
 The WB was taken in 2008 from a cut PVDF membrane. The original top and bottom edges of the exposition where cut to fit the image. Using the original WB image and doing different brightness contrast changes adjustments, the image showed different backgrounds on the areas highlighted by  Harengula jaguana (see the attached image). Therefore, although there are 2 white spots very similar, they are not identical and neither is the background surrounding.![file] , 
 #2 I agree with the original poster that there are unexpected similarities in certain regions. Could the authors please provide the original data? False color and enhanced contrast image shown below. *** ![file] , 
 #2 The similarities spotted by commenters #1 and #3 are too big to be explained with anything else than copy-paste of background. Any other explaination is impossible. ,