Upregulation of Ski in Fibroblast is Implicated in the Peroxisome Proliferator- Activated Receptor d-Mediated Wound Healing

Li, Jun; Li, Ping; Zhang, Yan; Li, Gongbo; He, Fengtian; Zhou, Yuan‐Guo; Yang, Kang; Dai, Shuang-Shuang

doi:10.1159/000341482

Cited by 14 publications

(12 citation statements)

References 49 publications

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“…It has reported that upregulation of Ski to promote fibroblast proliferation is implicated in wound healing (Li et al, 2012). And, increasing Ski protein level is capable of accelerating wound healing (Li et al, 2011).…”

Section: Discussionmentioning

confidence: 99%

RETRACTED: Ski diminishes TGF-β1-induced myofibroblast phenotype via up-regulating Meox2 expression

Chen

Ning

et al. 2014

Experimental and Molecular Pathology

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Section: Discussionmentioning

confidence: 99%

RETRACTED: Ski diminishes TGF-β1-induced myofibroblast phenotype via up-regulating Meox2 expression

Chen

Ning

et al. 2014

Experimental and Molecular Pathology

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“…As a versatile transcriptional regulator, it modulates the expression of multiple genes and is involved in many physiological and pathological processes [5]. Our previous studies confirmed the following: increased c-Ski expression at low TGF-β1 concentrations (from 2.5 pg/ml to 250 pg/ml) promotes fibroblast proliferation; reduced c-Ski expression at high TGF-β1 concentrations (> 2.5 ng/ml) inhibits proliferation [5]; and c-Ski achieves the optimal repair effect by promoting wound repair and inhibiting scar formation, but increased c-Ski expression has no significant effect on cell transformation induced by TGF-β1 [9][10][11][12]. High TGF-β1 concentrations negatively regulate c-Ski expression levels by inducing c-Ski degradation through the Smad2/ 3 signaling pathway [13,14], but the mechanism by which low TGF-β1 concentrations regulate c-Ski levels remains unclear.…”

Section: Introductionmentioning

confidence: 99%

The ERK/CREB pathway is involved in the c-Ski expression induced by low TGF-β1 concentrations during primary fibroblast proliferation

Liu

Peng

et al. 2018

Cell Cycle

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Increasing evidence has suggested that bidirectional regulation of cell proliferation is one important effect of TGF-β1 in wound healing. Increased c-Ski expression plays a role in promoting fibroblast proliferation at low TGF-β1 concentrations, but the mechanism by which low TGF-β1 concentrations regulate c-Ski levels remains unclear. In this study, the proliferation of rat primary fibroblasts was assessed with an ELISA BrdU kit. The mRNA and protein expression and phosphorylation levels of corresponding factors were measured by RT-qPCR, immunohistochemistry or Western blotting. We first found that low TGF-β1 concentrations not only promoted c-ski mRNA and protein expression in rat primary fibroblasts but also increased the phosphorylation levels of Extracellular Signal-Regulated Kinases (ERK) and cAMP response element binding (CREB) protein. An ERK kinase (mitogen-activated protein kinase kinase, MEK) inhibitor significantly inhibited ERK1/2 phosphorylation levels, markedly reducing c-Ski expression and CREB phosphorylation levels and abrogating the growth-promoting effect of low TGF-β1 concentrations. At the same time, Smad2/3 phosphorylation levels were not significantly changed. Taken together, these results suggest that the increased cell proliferation induced by low TGF-β1 concentrations mediates c-Ski expression potentially through the ERK/CREB pathway rather than through the classic TGF-β1/Smad pathway.

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“…c-Ski, a homologue of v-Ski in cells, is a versatile transcriptional regulator that is widely distributed in different cells, such as skeleton muscle cells, tumor cells, fibroblasts and VSMCs [13]–[17]. Previously, we have found it can suppress VSMC proliferation stimulated by transforming growth factor β (TGF-β) [18].…”

Section: Introductionmentioning

confidence: 99%

c-Ski Inhibits Autophagy of Vascular Smooth Muscle Cells Induced by oxLDL and PDGF

Zhao

Yang

et al. 2014

PLoS ONE

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Autophagy is increasingly being recognized as a critical determinant of vascular smooth muscle cell (VSMC) biology. Previously, we have demonstrated that c-Ski inhibits VSMC proliferation stimulated by transforming growth factor β (TGF-β), but it is not clear whether c-Ski has the similar protective role against other vascular injury factors and whether regulation of autophagy is involved in its protective effects on VSMC. Accordingly, in this study, rat aortic A10 VSMCs were treated with 40 µg/ml oxidized low-density lipoprotein (oxLDL) or 20 ng/ml platelet-derived growth factor (PDGF), both of which were autophagy inducers and closely related to the abnormal proliferation of VSMCs. Overexpression of c-Ski in A10 cells significantly suppressed the oxLDL- and PDGF- induced autophagy. This action of c-Ski resulted in inhibiting the cell proliferation, the decrease of contractile phenotype marker α-SMA expression while the increase of synthetic phenotype marker osteopontin expression stimulated by oxLDL or PDGF. Inversely, knockdown of c-Ski by RNAi enhanced the stimulatory effects of oxLDL or PDGF on A10 cell growth and phenotype transition. And further investigation found that inhibition of AKT phosphorylation to downregulate proliferating cell nuclear antigen (PCNA) expression, was involved in the regulation of autophagy and associated functions by c-Ski in the oxLDL- and PDGF-stimulated VSMCs. Collectively, c-Ski may play an important role in inhibiting autophagy to protect VSMCs against some harsh stress including oxLDL and PDGF.

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Upregulation of Ski in Fibroblast is Implicated in the Peroxisome Proliferator- Activated Receptor d-Mediated Wound Healing

Cited by 14 publications

References 49 publications

RETRACTED: Ski diminishes TGF-β1-induced myofibroblast phenotype via up-regulating Meox2 expression

RETRACTED: Ski diminishes TGF-β1-induced myofibroblast phenotype via up-regulating Meox2 expression

The ERK/CREB pathway is involved in the c-Ski expression induced by low TGF-β1 concentrations during primary fibroblast proliferation

c-Ski Inhibits Autophagy of Vascular Smooth Muscle Cells Induced by oxLDL and PDGF

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