Reduced hepatic stellate cell expression of Kruppel-like factor 6 tumor suppressor isoforms amplifies fibrosis during acute and chronic rodent liver injury.

ABSTRACT:

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Kruppel-like factor 6 (KLF6), a zinc finger transcription factor and tumor suppressor, is induced as an immediate-early gene during hepatic stellate cell (HSC) activation. The paradoxical induction of a tumor suppressor in HSCs during proliferation led us to explore the biology of wildtype KLF6 (KLF6(WT) ) and its antagonistic, alternatively spliced isoform KLF6(SV1) in cultured HSCs and animal models. The animal models generated include a global heterozygous KLF6 mouse (Klf6+/-), and transgenic mice expressing either hKLF6(WT) or hKLF6(SV1) under the control of the Collagen α2 (I) promoter to drive HSC-specific gene expression following injury. The rat Klf6 transcript has multiple splice forms that are homologous to those of the human KLF6 gene. Following a transient in

SUBMITTER: Ghiassi-Nejad Z 

PROVIDER: S-EPMC3522757 | biostudies-literature | 2013 Feb

REPOSITORIES: biostudies-literature