Wnt/β-catenin pathway forms a negative feedback loop during TGF-β1 induced human normal skin fibroblast-to-myofibroblast transition

Liu, Jiaqi; Wang, Yunchuan; Pan, Qiong; Su, Yingjun; Zhang, Zhan-Feng; Han, Juntao; Zhu, Xiaodong; Tang, Cui; Hu, Dahai

doi:10.1016/j.jdermsci.2011.09.012

Cited by 82 publications

(61 citation statements)

References 53 publications

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“…In this process, α-SMA was a critical marker of activated fibroblasts and plays essential roles in the pathogenesis of hypertrophic scars [25,26]. Besides, to our knowledge, an increase in production of TGF-β is one of the most important mechanisms in the pathogenesis of fibrosis [36,37]. TGF-β binds to and activates specific receptors (TGF-βRI, TGF-βRII) and thus stimulates the phosphorylation of Smad2 and Smad3 proteins, which in turn form complexes with Smad4.…”

Section: Taurine Decreased Expression Of Egr1 Both In Vivo and In Vitromentioning

confidence: 99%

Taurine Reduced Epidural Fibrosis in Rat Models after Laminectomy via Downregulating EGR1

Liu

Tang

Chen

et al. 2016

Cell Physiol Biochem

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Background/Aims: Epidural fibrosis, a common complication after laminectomy, has been demonstrated to be closely associated with poor surgical outcomes. Previous studies showed that taurine had remarkable anti-fibrotic effects on lung and liver fibrosis. We performed this study to investigate the effects of taurine in rat models of epidural fibrosis after laminectomy and to explore the potential molecular mechanism. Methods: Laminectomy was performed on each rat to establish epidural fibrosis model. After taurine treatment, Masson's trichrome and immunohistochemistry staining were used to examine epidural fibrosis. Cell viability was determined using the Cell Counting Kit-8 assay. Annexin V/Propidium Iodide double staining was performed to detect fibroblasts apoptosis. Microarray was adopted to identify significantly changed mRNAs. mRNA expression was measured by qRT-PCR. Lentivirus infection was performed to establish stable knockdown and overexpression cell lines. The expression of fibrosis-related proteins was determined via Western blot. Results: Taurine treatment markedly reduced laminectomy-induced epidural fibrosis in rat models. However, this effect of taurine was independent on TGF-β/Smad pathway, evidenced by no change in the expression of TGF-β and its receptors. Besides, taurine had almost no effect on cell apoptosis. Interestingly, taurine treatment significantly decreased expression of EGR1 (Early growth response protein 1), an enhancer of fibrosis, both in vivo and in vitro. Furthermore, overexpression of EGR1 increased activation of fibroblasts, while EGR1 knockdown achieved an opposite effect, indicating that EGR1 plays a key role in the inhibitory effect of taurine on TGF-β-induced fibrosis. Conclusions: Reduced epidural fibrosis in vivo and decreased activation of fibroblasts in vitro after taurine treatment was mediated by EGR1. Taurine promises to be a potential prevention for epidural fibrosis after laminectomy.

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Section: Taurine Decreased Expression Of Egr1 Both In Vivo and In Vitromentioning

confidence: 99%

Taurine Reduced Epidural Fibrosis in Rat Models after Laminectomy via Downregulating EGR1

Liu

Tang

Chen

et al. 2016

Cell Physiol Biochem

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“…In response to injury, fibroblasts rapidly proliferate, migrate, and differentiate to myofibroblasts 12. Canonical Wnt signaling has played a prominent role in fibroblast proliferation and differentiation 26, 27…”

Section: Components Of the Vasculature Systemmentioning

confidence: 99%

Atherosclerotic Calcification: Wnt Is the Hint

Albanese

Khan

Barratt

et al. 2018

JAHA

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“…Christiane Gras, 1* Dominica Ratuszny, 1* Catarina Hadamitzky, 2 Haijiao Zhang, 1 Rainer Blasczyk, 1 and Constança Figueiredo in wound granulation tissue (4). TGF-β1 coordinately induces the expression of collagen type I and α-smooth muscle actin (α-SMA), of which the latter has been widely used as a myofibroblast marker (3).…”

Section: Mir-145 Contributes To Hypertrophic Scarring Of the Skin Bymentioning

confidence: 99%

miR-145 Contributes to Hypertrophic Scarring of the Skin by Inducing Myofibroblast Activity

Gras

Ratuszny

Hadamitzky

et al. 2015

Mol Med

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Hyperthrophic scarring of the skin is caused by excessive activity of skin myofibroblasts after wound healing and often leads to functional and/or aesthetic disturbance with significant impairment of patient quality of life. MicroRNA (miRNA) gene therapies have recently been proposed for complex processes such as fibrosis and scarring. In this study, we focused on the role of miR-145 in skin scarring and its influence in myofibroblast function. Our data showed not only a threefold increase of miR-145 levels in skin hypertrophic scar tissue but also in transforming growth factor β1 (TGF-β1)-induced skin myofibroblasts compared with healthy skin or nontreated fibroblasts (p < 0.001). Consistent with the upregulation of miR-145 induced by TGF-β1 stimulation of fibroblasts, the expression of Kruppel-like factor 4 (KLF4) was decreased by 50% and α-smooth muscle actin (α-SMA) protein expression showed a threefold increase. Both could be reversed by miR-145 inhibition (p < 0.05). Restoration of KLF4 levels equally abrogated TGF-β1-induced α-SMA expression. These data demonstrate that TGF-β1 induces miR-145 expression in fibroblasts, which in turn inhibits KLF4, a known inhibitor of α-SMA, hence upregulating α-SMA expression. Furthermore, treatment of myofibroblasts with a miR-145 inhibitor strongly decreased their α-1 type I collagen expression, TGF-β1 secretion, contractile force generation and migration. These data demonstrate that upregulation of miR-145 plays an important role in the differentiation and function of skin myofibroblasts. Additionally, inhibition of miR-145 significantly reduces skin myofibroblast activity. Taken together, these results suggest that miR-145 is a promising therapeutic target to prevent or reduce hypertrophic scarring of the skin.

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Wnt/β-catenin pathway forms a negative feedback loop during TGF-β1 induced human normal skin fibroblast-to-myofibroblast transition

Cited by 82 publications

References 53 publications

Taurine Reduced Epidural Fibrosis in Rat Models after Laminectomy via Downregulating EGR1

Taurine Reduced Epidural Fibrosis in Rat Models after Laminectomy via Downregulating EGR1

Atherosclerotic Calcification: Wnt Is the Hint

miR-145 Contributes to Hypertrophic Scarring of the Skin by Inducing Myofibroblast Activity

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