MicroRNA-152-5p inhibits proliferation and migration and promotes apoptosis by regulating expression of Smad3 in human keloid fibroblasts

Pang, Qi; Wang, Yuming; Xu, Ming; Xu, Jialin; Xu, Shengquan; Yichen, Shen; Xu, Jinghong; Li, Rui

doi:10.5483/bmbrep.2019.52.3.278

Cited by 20 publications

(20 citation statements)

References 33 publications

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“…α-SMA, Collagen I and Collagen III were overexpressed in keloid fibroblasts, and α-SMA contributed to collagen gel contraction [27,28]. Overexpression of miR-152-5p suppressed human keloid fibroblasts development by downregulating Smad3 [30]. In our study, miR-590-3p was verified as a target of LINC01615.…”

Section: Discussionsupporting

confidence: 59%

Long noncoding RNA LINC01615 promotes keloid development via sponging miR-590-3p to regulate FGF2 expression

Zhang¹,

Xu²,

Yamagata³

et al. 2020

Preprint

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Background A keloid is a benign human skin tumor that resulted by fibrous overgrowths during wound healing. Long noncoding RNAs (lncRNAs) are indicated to involve in the development of keloid. However, the role of lncRNA LINC01615 in regulating keloid development and the underlying mechanism are still unknown. Methods The expression levels of LINC01615, miR-590-3p and fibroblast growth factor 2 (FGF2) mRNA were detected by quantitative real-time polymerase chain reaction (qRT-PCR). The protein levels of apoptosis-related proteins, α-smooth muscle actin (α-SMA), collagens and FGF2 were measured by western blot. The effect of LINC01615 on keloid development was assessed by cell proliferation, apoptosis and collagen deposition of keloid fibroblasts which were determined by Cell Counting Kit-8 (CCK-8), flow cytometry assay and the protein levels of collagens, respectively. The relationships between LINC01615 and miR-590-3p, miR-590-3p and FGF2 were predicated by online software and confirmed by dual-luciferase reporter assay and RNA pull-down assay. Results We first found that LINC01615 was upregulated in keloid tissues and fibroblasts, and LINC01615 promoted cell proliferation and collagen deposition and suppressed apoptosis in keloid fibroblasts. LINC01615 targeted miR-590-3p and downregulated miR-590-3p expression, and overexpression of miR-590-3p inhibited the development of keloid. Then, FGF2 was identified as a target of miR-590-3p. LINC01615 facilitated keloid development via regulating FGF2 expression through miR-590-3p. Conclusion Our study demonstrated that LINC01615 contributed to keloid development via the miR-590-3p/FGF2 axis.

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Section: Discussionsupporting

confidence: 59%

Long noncoding RNA LINC01615 promotes keloid development via sponging miR-590-3p to regulate FGF2 expression

Zhang¹,

Xu²,

Yamagata³

et al. 2020

Preprint

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“…The top PGE 2 -upregulated miRNA, miR–129-5p, exhibits antifibrotic actions in dermal fibroblasts by targeting COL1A1 ( 49 ). Furthermore, FGF2 upregulated the antifibrotic miR–29b-3p/5p, miR–152-5p, and let-7a-3p ( 5 , 50 , 51 ), while downregulating the profibrotic miR–145-3p ( 52 ). Other profibrotic- and antifibrotic-associated miRNAs — including miR-21 ( 53 ) and miR–27a-3p/miR–27b-3p ( 54 ) — were detected in high abundance in our analysis but were not differentially regulated by either treatment ( Supplemental Table 5 ).…”

Section: Resultsmentioning

confidence: 99%

Myofibroblast dedifferentiation proceeds via distinct transcriptomic and phenotypic transitions

Fortier¹,

Penke²,

King³

et al. 2021

JCI Insight

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Myofibroblasts are the major cellular source of collagen, and their accumulationvia differentiation from fibroblasts and resistance to apoptosis-is a hallmark of tissue fibrosis. Clearance of myofibroblasts by de-differentiation and restoration of apoptosis sensitivity has the potential to reverse fibrosis. Prostaglandin E2 (PGE2) and mitogens such as FGF2 have each been shown to de-differentiate myofibroblasts, but the resultant cellular phenotypes have neither been comprehensively characterized nor compared. Here we show that PGE2 elicited de-differentiation of human lung myofibroblasts via cAMP/PKA while FGF2 utilized MEK/ERK. The two mediators yielded transitional cells with distinct transcriptomes, with FGF2 promoting but PGE2 inhibiting proliferation and survival. The gene expression pattern in fibroblasts isolated from the lungs of mice undergoing resolution of experimental fibrosis resembled that of myofibroblasts treated with PGE2 in vitro. We conclude that myofibroblast dedifferentiation can proceed via distinct programs exemplified by treatment with PGE2 and FGF2, with that occurring in vivo most closely resembling the former.

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“…In addition, miR-152-5p and miR-637 had been demonstrated to be decreased in KFs. The upregulation of miR-152-5p played an irreplaceable role in putting off the progression of fibrosis in keloid by inhibiting proliferation, migration, and promoting apoptosis through the Erk1/2 and Akt pathways [ 78 ]. Interestingly, both miR-637 mimic and silencing Smad3 obtained consistent results in KFs, thereby confirmed that Smad3 was the direct target of miR-152-5p and miR-637 [ 79 ].…”

Section: Epigenetic Modification Mechanisms In Keloidmentioning

confidence: 99%

Epigenetic modification mechanisms involved in keloid: current status and prospect

Ren

Hou

et al. 2020

Clin Epigenet

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Keloid, a common dermal fibroproliferative disorder, is benign skin tumors characterized by the aggressive fibroblasts proliferation and excessive accumulation of extracellular matrix. However, common therapeutic approaches of keloid have limited effectiveness, emphasizing the momentousness of developing innovative mechanisms and therapeutic strategies. Epigenetics, representing the potential link of complex interactions between genetics and external risk factors, is currently under intense scrutiny. Accumulating evidence has demonstrated that multiple diverse and reversible epigenetic modifications, represented by DNA methylation, histone modification, and non-coding RNAs (ncRNAs), play a critical role in gene regulation and downstream fibroblastic function in keloid. Importantly, abnormal epigenetic modification manipulates multiple behaviors of keloid-derived fibroblasts, which served as the main cellular components in keloid skin tissue, including proliferation, migration, apoptosis, and differentiation. Here, we have reviewed and summarized the present available clinical and experimental studies to deeply investigate the expression profiles and clarify the mechanisms of epigenetic modification in the progression of keloid, mainly including DNA methylation, histone modification, and ncRNAs (miRNA, lncRNA, and circRNA). Besides, we also provide the challenges and future perspectives associated with epigenetics modification in keloid. Deciphering the complicated epigenetic modification in keloid is hopeful to bring novel insights into the pathogenesis etiology and diagnostic/therapeutic targets in keloid, laying a foundation for optimal keloid ending.

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MicroRNA-152-5p inhibits proliferation and migration and promotes apoptosis by regulating expression of Smad3 in human keloid fibroblasts

Cited by 20 publications

References 33 publications

Long noncoding RNA LINC01615 promotes keloid development via sponging miR-590-3p to regulate FGF2 expression

Long noncoding RNA LINC01615 promotes keloid development via sponging miR-590-3p to regulate FGF2 expression

Myofibroblast dedifferentiation proceeds via distinct transcriptomic and phenotypic transitions

Epigenetic modification mechanisms involved in keloid: current status and prospect

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