A novel regulatory function for miR-29a in keloid fibrogenesis

Zhang, G.-Y.; Wu, Li; Liao, Tian; Chen, G.-C.; Chen, Y.-H.; Zhao, Yixuan; Chen, S.-Y.; Wang, A.-Y.; Lin, Kuan‐Yu; Lin, Damu; Yang, Jingquan; Gao, Weiyang; Li, Q.-F.

doi:10.1111/ced.12734

Cited by 45 publications

(41 citation statements)

References 10 publications

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“…87 Recently, miR-29a, another miRNA with decreased expression in keloid fibroblasts, was also shown to negatively regulate type I/III collagen expression. 88 Further miRNAs involved in pathological scar formation include miR-21, which promotes fibroblast proliferation in HTS formation and in keloids; miR-200b and miR-199a-5p, which inhibit fibroblast proliferation; and miR-10a and -181c, which regulate collagen I generation (Table 3). 89–95 …”

Section: Discussion Of Findings and Relevant Literaturementioning

confidence: 99%

Non-Coding RNAs: New Players in Skin Wound Healing

2017

Advances in Wound Care

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Significance: Wound healing is a basic physiological process that is utilized to keep the integrity of the skin. Impaired wound repair, such as chronic wounds and pathological scars, presents a major health and economic burden worldwide. To date, efficient targeted treatment for these wound disorders is still lacking, which is largely due to our limited understanding of the biological mechanisms underlying these diseases. Research driven around discovering new therapies for these complications is, therefore, an urgent need.Recent Advances: The vast majority of the human genome is transcribed to RNAs that lack protein-coding capacity. Intensive research in the recent decade has revealed that these non-coding RNAs (ncRNAs) function as important regulators of cellular physiology and pathology, which makes them promising therapeutic and diagnostic entities.Critical Issues: A class of short ncRNAs, microRNAs, has been found to be indispensable for all the phases of skin wound healing and plays important roles in the pathogenesis of wound complications. The role of long ncRNAs (lncRNA) in skin wound healing remains largely unexplored. Recent studies revealed the essential role of lncRNAs in epidermal differentiation and stress response, indicating their potential importance for skin wound healing, which warrants future research.Future Directions: An investigation of ncRNAs will add new layers of complexity to our understanding of normal skin wound healing as well as to the pathogenesis of wound disorders. Development of ncRNA-based biomarkers and treatments is an interesting and important avenue for future research on wound healing.

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Section: Discussion Of Findings and Relevant Literaturementioning

confidence: 99%

Non-Coding RNAs: New Players in Skin Wound Healing

2017

Advances in Wound Care

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“…Keloids generally occur following an abnormal wound healing; however, the pathogenesis remains unclear (61). Zhang et al (62) determined that all miR-29 family members are expressed in keloid fibroblasts (KFs) and fresh skin biopsy specimens (obtained 24-48 h after surgery) and, in particular, miR-29a is highly expressed in KFs. The authors also evaluated the interaction of miR-29a and collagen type III α1 chain (COL3α1) and demonstrated that miR-29a directly regulates enhancement of collagen production.…”

Section: Keloidsmentioning

confidence: 99%

“…The authors also evaluated the interaction of miR-29a and collagen type III α1 chain (COL3α1) and demonstrated that miR-29a directly regulates enhancement of collagen production. Furthermore, in normal fibroblasts, miR-29a directly regulates collagen production via affecting TGF-β expression (62). In another study, Liu et al (63) used microarray analysis for comparative miRNA profiling between keloid tissue and normal skin tissue samples.…”

Section: Keloidsmentioning

confidence: 99%

Role of the microRNA-29 family in fibrotic skin diseases

et al. 2017

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Abstract. Fibrotic skin diseases are characterized by the accumulation of collagen. The hallmarks of fibrotic skin diseases are unbalanced fibroblast proliferation and differentiation, extracellular matrix production and transforming growth factor-β signalling. Numerous studies have investigated the possibility that microRNAs (miRNAs or miRs) are involved in the pathogenesis of certain fibrotic diseases, including skin, heart, lung and liver diseases. miRNAs are a class of small non-coding RNAs, which modify gene expression by binding to target messenger RNA (mRNA) and blocking the translation or inducing the degradation of target mRNA. The biological relevance of miRNAs has been investigated in physiological and pathological conditions, and there is increasing evidence that the miR-29 family is associated with fibrotic diseases. The aim of the present review is to provide an up-to-date summary of current knowledge on the latest developments associated with the miR-29 family and fibrotic skin diseases.

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“…MiRNAs partly suppress the expression of target genes through binding to their 3′ untranslated regions (UTR) and consequently influence a variety of physiological and pathological processes, including proliferation, metabolism, apoptosis, and invasion [4][5][6]. Emerging evidence has shown that miRNAs contribute to hypertrophic scarring or keloid formation [7][8][9]. Earlier, Zhang et al [7] reported that miR-29a directly regulates the translation of various ECM mRNAs, such as the collagen superfamily, in fibrogenesis of keloids, suggesting utility as a novel marker for keloid.…”

Section: Introductionmentioning

confidence: 99%

“…Emerging evidence has shown that miRNAs contribute to hypertrophic scarring or keloid formation [7][8][9]. Earlier, Zhang et al [7] reported that miR-29a directly regulates the translation of various ECM mRNAs, such as the collagen superfamily, in fibrogenesis of keloids, suggesting utility as a novel marker for keloid. Downregulation of miR-125b in psoriatic skin has been shown to contribute to keratinocyte hyperproliferation [8].…”

Section: Introductionmentioning

confidence: 99%

MiR-181a Targets PHLPP2 to Augment AKT Signaling and Regulate Proliferation and Apoptosis in Human Keloid Fibroblasts

Rang

Wang

Pang

et al. 2016

Cell Physiol Biochem

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Background/Aims: Keloids are fibrous overgrowths induced by cutaneous injury. MicroRNAs (miRNAs) have recently emerged as post-transcriptional gene repressors and participants in a diverse array of pathophysiological processes leading to skin disease. The purpose of the current study was to explore the precise functions of miR-181a in human keloid development and the underlying mechanisms. Methods: A miRNA microarray analysis was performed to compare expression profiles between keloid and normal skin tissues. Quantitative real-time PCR was conducted to estimate miR-181a expression. Cell proliferation was determined using the cell counting kit-8 (CCK-8) and 5-ethynyl-2-deoxyuridine (EdU) assays, and cell cycle and apoptosis were detected with flow cytometry. Direct targets of miR-181a were identified using the luciferase reporter assay. Results: miR-181a was significantly upregulated in human keloid tissues and fibroblasts, compared with their control counterparts. Overexpression of miR-181a enhanced keloid fibroblast DNA synthesis and proliferation and inhibited apoptosis, whereas miR-181a suppression triggered the opposite effects. Moreover, miR-181a suppressed the expression of PH domain leucine-rich repeat protein phosphatase 2 (PHLPP2) through direct interactions with its 3′UTR region and subsequently enhanced AKT activation. Overexpression of PHLPP2 without its 3′UTR attenuated the effects of miR-181a on cell proliferation and apoptosis in keloid fibroblast cells. Furthermore, miR-181a mimics increased normal skin fibroblast proliferation. Conclusions: Our results highlight a novel pathway mediated by miR-181a, which may be effectively used as a therapeutic target for treatment of keloids.

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A novel regulatory function for miR-29a in keloid fibrogenesis

Abstract: These findings show that miR-29a exerts as a novel regulator in the fibrogenesis of keloid, suggesting that miR-29a might be a novel marker for keloid.

Cited by 45 publications

References 10 publications

Non-Coding RNAs: New Players in Skin Wound Healing

Non-Coding RNAs: New Players in Skin Wound Healing

Role of the microRNA-29 family in fibrotic skin diseases

MiR-181a Targets PHLPP2 to Augment AKT Signaling and Regulate Proliferation and Apoptosis in Human Keloid Fibroblasts

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