Repression of Myoblast Proliferation and Fibroblast Growth Factor Receptor 1 Promoter Activity by KLF10 Protein

Parakati, Rajini; DiMario, Joseph X.

doi:10.1074/jbc.m113.457648

Cited by 35 publications

(27 citation statements)

References 33 publications

(60 reference statements)

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“…9). Additionally, some genes involved in the smooth muscle maturation and skeletal myogenesis, as reported in previous studies (31)(32)(33)(34)(35)(36), were also found to be differentially expressed in CK14-Cre;Shh fl/fl mutant mice ( Fig. 9).…”

Section: Discussionsupporting

confidence: 78%

Loss of sonic hedgehog gene leads to muscle development disorder and megaesophagus in mice

et al. 2018

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Sonic hedgehog ( Shh) is crucial for organogenesis in the foregut. This study investigated the function of Shh at the late-gestational stage; during which, the esophagus continues to differentiate. We established cytokeratin 14 ( CK14)-Cre;Shh mice in which the down-regulation of Shh in the epithelium occurred at approximately the same time as esophageal muscle conversion. Hematoxylin and eosin and immunohistochemical staining, with antibodies against keratin 14, Shh, patched 1 (Ptch1), Gli1, proliferating cell nuclear antigen (PCNA), α-smooth muscle actin (αSMA), high-molecular-weight caldesmon (hCD), myogenin, paired box 7 (Pax7), β3-tubulin, and protein gene product 9.5 (PGP9.5), was performed to detect specific tissue dysplasia. Organ culture was conducted in vitro, and total mRNA was extracted to determine the transcriptional dysregulation. The esophagus of CK14-Cre;Shh mice developed into an independent tube with an obvious dilatation at postnatal d 0.5. The number of cell layers and the expression of PCNA were decreased in mutant mice, compared with those in wild-type mice. The expression of hCD declined progressively in the middle, distal, and lower esophageal sphincter levels of the mutant esophagus from embryonic d 17.5, compared with the expression in wild-type littermates. Pax7 accumulation and myogenin reduction in mutant mice indicated that esophageal skeletal-myoblast progression was blocked. RNA sequencing analysis revealed a significant down-regulation of genes involved in proliferation and muscular motivation in CK14-Cre;Shh mice. Thus, loss of Shh at the late-gestational stage leads to megaesophagus with reduced proliferation and a muscle development disorder in mice.-Jia, X., Min, L., Zhu, S., Zhang, S., Huang, X. Loss of sonic hedgehog gene leads to muscle development disorder and megaesophagus in mice.

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Section: Discussionsupporting

confidence: 78%

Loss of sonic hedgehog gene leads to muscle development disorder and megaesophagus in mice

et al. 2018

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“…It has been found that the KLF10 protein could repress the proliferation of myoblasts and the activity of fibroblast growth factor receptor 1 promoter. 19 KLF3 regulates the expression of muscle-specific genes through binding to their promoters. 20 Many studies have shown that KLF6 can regulate various physiological and pathological processes, such as homeostasis, 21 lipid metabolism, adipocyte proliferation, 22 and proliferation and apoptosis of bovine muscle cells 23 and lung cancer cells.…”

Section: Introductionmentioning

confidence: 99%

MiR‐543 regulates myoblast proliferation and differentiation of C2C12 cells by targeting KLF6

Kang

Xing

Chen

et al. 2020

J of Cellular Biochemistry

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MicroRNA-543 (miR-543) has been found to play a suppressive role in various human cancers in many studies, whereas the specific functions of miR-543 in muscle development remain poorly understood. Here, we found that the expression of miR-543 was high in skeletal muscle and increased during the differentiation of C2C12 cells. Overexpression of miR-543 repressed C2C12 cell proliferation and promoted differentiation, while knockdown of miR-543 expression produced the opposite results. During myogenesis, we predicted and verified that Krüppel-like factor 6 (KLF6), a suppressor of multiple tumor cells, was a target gene of miR-543. Then, miR-543 was found to specifically target KLF6 and repress its expression. Besides this, knockdown of KLF6 promoted the differentiation but inhibited the proliferation of C2C12 cells. Si-KLF6 can rescue the influence of miR-543 inhibitor on C2C12 cell differentiation. Our results indicate a new regulatory mechanism of miR-543 on KLF6 expression and suggest the possibility of using the miR-543/KLF6 pathway as a potential target for studying myogenesis.

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“…This effect on FGFR1 gene expression generally correlates with the altered proliferation and differentiation of C 2 C 12 cells overexpressing KLF10. 29,30 KLF10 also mediates TGF-b signaling through transcriptional regulation of genes encoding SMAD isoforms. KLF10 represses SMAD7 gene expression, but conversely activates SMAD2 gene expression.…”

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confidence: 99%

KLF10 Gene Expression Modulates Fibrosis in Dystrophic Skeletal Muscle

DiMario

2018

The American Journal of Pathology

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Dystrophic skeletal muscle is characterized by fibrotic accumulation of extracellular matrix components that compromise muscle structure, function, and capacity for regeneration. Tissue fibrosis is often initiated and sustained through transforming growth factor-β (TGF-β) signaling, and Krüppel-like factor 10 (KLF10) is an immediate early gene that is transcriptionally activated in response to TGF-β signaling. It encodes a transcriptional regulator that mediates the effects of TGF-β signaling in a variety of cell types. This report presents results of investigation of the effects of loss of KLF10 gene expression in wild-type and dystrophic (mdx) skeletal muscle. On the basis of RT-PCR, Western blot, and histological analyses of mouse tibialis anterior and diaphragm muscles, collagen type I (Col1a1) and fibronectin gene expression and protein deposition were increased in KLF10 mice, contributing to increased fibrosis. KLF10 mice displayed increased expression of genes encoding SMAD2, SMAD3, and SMAD7, particularly in diaphragm muscle. SMAD4 gene expression was unchanged. Expression of the extracellular matrix remodeling genes, MMP2 and TIMP1, was also increased in KLF10-deficient mouse muscle. Histological analyses and assays of hydroxyproline content indicated that the loss of KLF10 increased fibrosis. Dystrophic KLF10-null mice also had reduced grip strength. The effects of loss of KLF10 gene expression were most pronounced in dystrophic diaphragm muscle, suggesting that KLF10 moderates the fibrotic effects of TGF-β signaling in chronically damaged regenerating muscle.

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Repression of Myoblast Proliferation and Fibroblast Growth Factor Receptor 1 Promoter Activity by KLF10 Protein

Cited by 35 publications

References 33 publications

Loss of sonic hedgehog gene leads to muscle development disorder and megaesophagus in mice

Loss of sonic hedgehog gene leads to muscle development disorder and megaesophagus in mice

MiR‐543 regulates myoblast proliferation and differentiation of C2C12 cells by targeting KLF6

KLF10 Gene Expression Modulates Fibrosis in Dystrophic Skeletal Muscle

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