Functional role of KLF10 in multiple disease processes

Abstract

Since the discovery by this laboratory of the zinc finger transcription factor, KLF10, a member of the Krüppel-like family of transcription factors, there have been multiple publications regarding its functions and its immediate family members, in numerous cell types. KLF10 has been shown to be rapidly induced by TGFβ1, 2, 3, E2, epidermal growth factor, and bone morphogenetic protein-2. TGFβ inducible early gene-1 activates the TGFβ-Smad signaling pathway via repression of Smad 7 expression and activation of Smad 2 expression and activity. Overall, KLF10 has been implicated in cell differentiation, as a target gene for a variety of signaling pathways, and in serving as a potential marker for human diseases such as breast cancer, cardiac hypertrophy, and osteoporosis. Like other KLF members, KLF10 is expressed in specific cell types in numerous tissues and is known to be involved in repressing cell proliferation and inflammation as well as inducing apoptosis similar to that of TGFβ KLF10 binds to Sp-1-GC rich DNA sequences and can activate or repress the transcription of a number of genes. Overall, KLF10 has been shown to play a major role in the TGFβ inhibition of cell proliferation and inflammation and induction of apoptosis, and its overexpression in human osteoblasts and pancreatic carcinoma cells mimics the actions of TGFβ.

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

“…3A). KLF10 has been reported to enhance Smad2 expression (10), and this decrease may be a cause for KLF10 gene ablation in the KO mice. Unlike that of Smad2, the expression of Smad3 (a co-Smad) increased from 48 h post-PH in the KLF10-KO mice (Fig.…”

“…Smad2, Smad7 and p21, which have previously been reported to be target genes of KLF10 (10,17), and Smad3, Smad4, TGF-β1, TGF-βR1, TGF-βR2, p15, p21, cMyc and cyclin D1, which are mediators or target genes of the TGF-β/Smad pathway (14,15), were analyzed by RT-qPCR. Smad2, one of the R-Smads, exhibited significantly lower transcription levels in KLF10-KO mice compared with WT mice from 24 h post-PH (24 h, P= 0.034; 48 h, P= 0.036; 72 h, P= 0.028; Fig.…”

“…KLF10 is known as a potential antiproliferative gene; however, to the best of our knowledge, there are no reports on the role of KLF10 in liver regeneration (10,21). In the present study, to elucidate the role of the KLF10 gene in liver regeneration following tissue loss, molecular and histopathological analyses were conducted using KLF10-knockout (KO) mice following a PH that removed two-thirds of the liver.…”

“…Among these, the TGF-β/Smad pathway is reported to suppress cellular proliferation and to regulate numerous biological processes; however, the responses to TGF-β differ according to cell or tissue type and the microenvironment (8)(9)(10).…”

“…KLF10 may enhance Smad2, p21 and plasminogen activator inhibitor-1 expression, and repress the transcription of the Smad7 gene. KLF10 also plays important roles in numerous biological processes, and it has been reported to inhibit proliferation and induce apoptosis in several cell types (10,17,18). However, the role of KLF10 in various pathophysiological conditions remains unclear.…”