Knockout of kruppel-like factor 10 suppresses hepatic cell proliferation in a partially hepatectomized mouse model

The liver has marked regenerative capabilities, and numerous signaling pathways are involved in liver regeneration. The transforming growth factor-beta (TGF-beta)/Smad pathway, which is also involved in liver regeneration, regulates numerous biological processes. Kruppel-like factor 10 (KLF10) has been reported to activate the TGF-beta/Smad signaling pathway; however, the exact functions of KLF10 under various pathophysiological conditions remain unclear. In the present study, the role of KLF10 in liver regeneration following partial hepatectomy (PH) was investigated using KLF10-knockout (KO) mice. KLF10-KO mice exhibited lower liver/body weight ratios and 5-bromo-2-deoxy-uridine labeling indices compared with wild-type (WT) mice, and significant differences (P=0.028) were obtained at 72 h after PH. To understand the causes of the gross and histopathological findings, the expression levels of the components of the TGF-beta/ Smad pathway were examined using reverse transcription-quantitative polymerase chain reaction and western blot analysis. The mRNA and protein levels of Smad3, p15, TGF-beta 1 and TGF-beta receptor 1 were significantly increased, while those of cMyc and cyclin D1 (proliferation-associated genes) were significantly lower in the liver tissues of the KLF10-KO mice compared with those of the WT mice at 72 h post-PH. These results indicated that KLF10-KO may exhibit antiproliferative effects on liver regeneration following PH, through strengthening the TGF-beta/Smad signaling pathway in a delayed manner.