TGF-β1 promotes scar fibroblasts proliferation and transdifferentiation via up-regulating MicroRNA-21

Liu, Ying; Li, Yue; Li, Ning; Teng, Wen Yuan; Wang, Min; Zhang, Yingbo; Xiao, Zhibo

doi:10.1038/srep32231

Cited by 141 publications

(115 citation statements)

References 35 publications

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“…It seems that the mechanism of the effect of this factor is through the increase of the expression of micro R 21 and through PTEN/Akt pathway. It has also been shown that this factor inhibits the pathway of NOTCH/Jagged1 and so causes scar inhibition (Jagadeesan & Bayat, ; Lichtman et al, ; Liu et al, ; Penn, Grobbelaar, & Rolfe, ). Therefore, reducing TGFβ1 can be a strategy to prevent scarring and the same has been suggested by various studies.…”

Section: Discussionmentioning

confidence: 99%

“…There are few strategies to prevent or to treat scarring that were not so successful (Lichtman, Otero‐Vinas, & Falanga, ). Growth factors have vital roles in this process, for example, it seems that overexpression of TGFβ1 may mediate fibrosis in wound while bFGF may promote scarless healing and reduce scarring in this process(Akita, Akino, & Hirano, ; Liu et al, ; Shah, Foreman, & Ferguson, ; Shi et al, ; Song, Bian, Lai, Chen, & Zhao, ; Wang et al, ). The usage of medicinal plants to treat wound has a long history; different effective components and biological balance of their compounds are sometimes more effective and have fewer side effects in treatment of wound, one of these plants is Achillea (Akkol, Koca, Pesin, & Yilmazer, ; Ghobadian et al, ; Khosra et al, ).…”

Section: Introductionmentioning

confidence: 99%

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Achillea biebersteinni Afan may inhibit scar formation: In vitro study

Hadipour

Baharvand

2019

Molec Gen & Gen Med

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Background One of the major problems in wound healing is scar formation; however, there are few ways to prevent or treat it. Different species of Achillea are used to treat wounds in folk medicine from the past but there are few studies on the effect of it on wound healing and inhibition of scar formation. The aim of this study was to investigate the effect of Achillea biebersteinii Afan hydroethanolic extract on the expression of TGFβ1 and bFGF as effective growth factors of wound healing in mouse embryonic fibroblast cells. Methods Mouse embryonic fibroblast cells were exposed to different concentrations of Achillea extract at two different time (12 and 24 hr); the expression of TGFβ1 and bFGF was performed by real‐time‐PCR and ELISA at the level of gene and protein. Results It was observed that the plant extract at 5 and 10 µg/ml downregulated the expression of TGFβ1 and upregulated the expression of bFGF at the level of gene and protein. Conclusion The results showed that the pattern of changes in the expression of TGFβ1 and bFGF by Achillea biebersteinni Afan extract may inhibit scar formation.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Achillea biebersteinni Afan may inhibit scar formation: In vitro study

Hadipour

Baharvand

2019

Molec Gen & Gen Med

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“…Liu et al [37] demonstrated that miR-21 was required for TGF-β-induced fibrogenic EMT in hepatocytes. miR-21 was overexpressed in human keloid fibroblasts induced by TGF-β1 [41]. Besides, miR-21 could promote TGF-β1-induced EMT in gastric cancer cells [42] and promotes breast cancer progression and chemoresistance through TGF-β1 stimulation [43].…”

Section: Discussion/conclusionmentioning

confidence: 99%

“…Recently, miR-21 has been ascribed a crucial role in the regulation of cellular activity during physiological and pathological processes [31]. miR‑21 is widely expressed and has been found to be increased in organs and tissues which have suffered fibrogenesis or remodeling, including the heart [32], kidney [33], lung [34], asthmatic airways [35, 36], liver [37, 38], skin [39-41], and tumor tissue [42, 43]. Studies revealed that enhanced miR-21 expression is involved in the progression of lung fibrosis, and TGF-β1 plays an important role in mediating increased miR-21 expression [34, 44].…”

Section: Introductionmentioning

confidence: 99%

TGF-β1 Induces Epithelial-Mesenchymal Transition of Chronic Sinusitis with Nasal Polyps through MicroRNA-21

Zhu

et al. 2019

Int Arch Allergy Immunol

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Objectives: To characterize the epithelial-mesenchymal transition (EMT) in chronic rhinosinusitis with nasal polyps (CRSwNP) and to investigate the mechanism by which microRNA-21 (miR-21) regulates EMT in CRSwNP. Method: (1) Tissue experiments: Mucosa tissues were collected from 13 patients with CRSwNP and 12 patients with CRS without nasal polyps (CRSsNP), as well as 11 patients without CRS (controls). Protein localization and quantification were achieved by immunofluorescence staining and Western blotting, involving the epithelial marker protein E-cadherin and the mesenchymal marker proteins α-smooth muscle actin (α-SMA), fibronectin, and vimentin. Quantitative RT-PCR was used to detect the relative expression levels of miR-21 and TGF-β1 mRNAs. (2) Cellular experiments: Primary human nasal epithelial cells (PHNECs) treated with TGF-β1, or TGF-β1 with miR-21 inhibitor, or miR-21 mimics alone were observed for morphology changes under a phase-contrast microscope. The expression levels of epithelial/mesenchymal marker proteins were determined as aforementioned. PTEN and phosphorylated Akt were detected by Western blotting. Results: (1) Tissue experiments: Compared with the CRSsNP and control groups, the expression of E-cadherin was downregulated in the CRSwNP group, whereas the expression of TGF-β1, α-SMA, fibronectin, and vimentin was upregulated. The expression levels of miR-21 and TGF-β1 mRNAs in CRSwNP were significantly higher than those in CRSsNP and controls. (2) Cellular experiments: TGF-β1 induced EMT-like transformation in PHNECs, featured by changes in cell morphology and upregulation of mesenchymal proteins and miR-21. The miR-21 inhibitor, as well as the Akt-specific inhibitor, suppressed TGF-β1-induced EMT. Mechanically, downregulation of miR-21 resulted in increased PTEN and decreased Akt phosphorylation. Furthermore, overexpression of miR-21 had the opposite effects. Conclusions: Our findings suggest that the TGF-β1-miR-21-PTEN-Akt axis may contribute to the pathogenesis of CRSwNP. miR-21 might be a reliable target for treating nasal polyp genesis through EMT suppression. Moreover, miR-21 inhibitors could be a novel class of antipolyp drug that modulates PTEN expression and Akt activation. In addition, further investigation regarding the reason underlying miR-21 overexpression in CRSwNP could provide a molecular target for novel treatment strategies for nasal polyposis.

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“…TGF-β1 directly promotes the proliferation and differentiation of dermal fibroblasts, encouraging collagen formation via the miR-21 and PTEN/ Akt signaling pathway [17]. It can also inhibit DNA methyltransferase, thereby inducing demethylation of the promoter region of collagen genes and upregulation of collagen production [18].…”

Section: Discussionmentioning

confidence: 99%

Effects of Initiation Time of Glycemic Control on Skin Collagen Recovery in Streptozotocin-Induced Diabetic Rats

et al. 2018

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Background: Diabetes damages the collagen in the skin. No study has investigated the relationship between the treatment initiation time and the degree of collagen recovery. This study aimed to evaluate the effects of the initiation time of glycemic control on collagen recovery and to determine the basic molecules mediating the process. Methods: Streptozotocin-induced diabetic rats were divided into five groups: normal controls (C), those with untreated diabetes (DM), and those with diabetes treated with daily insulin injections from 7 weeks (7W), 10 weeks (10W), and 13 weeks (13W) after diabetes induction. The levels of collagen and several molecules were compared among skin tissues collected at 14 weeks. Results: The amounts of total collagen, collagen 1, and collagen 3 were significantly lower in DM than in C. Among the treated groups, recovery reaching normal levels was only observed in 7W and 10W. The earlier the treatment began, the greater was the collagen recovery. Similar to that of collagen, the expression of transforming growth factor-β1 (TGF-β1), vascular endothelial growth factor (VEGF), and insulin-like growth factor 1 receptor (IGF-1R) significantly decreased in DM compared with that in C. Higher recovery of TGF-β1 and VEGF was detected in groups with earlier treatment, whereas the IGF-1R level was identically elevated in all treated groups. The results suggest that these molecules affect collagen recovery at different time points during glycemic control. Conclusion: The initiation time of glycemic control is expected to have a considerable effect on collagen recovery in the diabetic skin through modulation of TGF-β1, VEGF, and IGF-1R.

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TGF-β1 promotes scar fibroblasts proliferation and transdifferentiation via up-regulating MicroRNA-21

Cited by 141 publications

References 35 publications

Achillea biebersteinni Afan may inhibit scar formation: In vitro study

Achillea biebersteinni Afan may inhibit scar formation: In vitro study

TGF-β1 Induces Epithelial-Mesenchymal Transition of Chronic Sinusitis with Nasal Polyps through MicroRNA-21

Effects of Initiation Time of Glycemic Control on Skin Collagen Recovery in Streptozotocin-Induced Diabetic Rats

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