title: MicroRNA-143-3p inhibits hyperplastic scar formation by targeting connective tissue growth factor CTGF/CCN2 via the Akt/mTOR pathway.
abstract: Post-traumatic hypertrophic scar (HS) is a fibrotic disease with excessive extracellular matrix (ECM) production, which is a response to tissue injury by fibroblasts. Although emerging evidence has indicated that miRNA contributes to hypertrophic scarring, the role of miRNA in HS formation remains unclear. In this study, we found that miR-143-3p was markedly downregulated in HS tissues and fibroblasts (HSFs) using qRT-PCR. The expression of connective tissue growth factor (CTGF/CCN2) was upregulated both in HS tissues and HSFs, which is proposed to play a key role in ECM deposition in HS. The protein expression of collagen I (Col I), collagen III (Col III), and α-smooth muscle actin (α-SMA) was obviously inhibited after treatment with miR-143-3p in HSFs. The CCK-8 assay showed that miR-143-3p transfection reduced the proliferation ability of HSFs, and flow cytometry showed that either early or late apoptosis of HSFs was upregulated by miR-143-3p. In addition, the activity of caspase 3 and caspase 9 was increased after miR-143-3p transfection. On the contrary, the miR-143-3p inhibitor was demonstrated to increase cell proliferation and inhibit apoptosis of HSFs. Moreover, miR-143-3p targeted the 3'-UTR of CTGF and caused a significant decrease of CTGF. Western blot demonstrated that Akt/mTOR phosphorylation and the expression of CTGF, Col I, Col III, and α-SMA were inhibited by miR-143-3p, but increased by CTGF overexpression. In conclusion, we found that miR-143-3p inhibits hypertrophic scarring by regulating the proliferation and apoptosis of human HSFs, inhibiting ECM production-associated protein expression by targeting CTGF, and restraining the Akt/mTOR pathway.
authors.affiliation: Department of Burn and Plastic Surgery, The Third Affiliated Hospital, Xi'an Jiaotong University Medical College, Xi'an, 710068, China.
authors.forename: Shengzhi
authors.initials: S
authors.lastname: Mu
authors.affiliation: Department of Neurology, The Third Affiliated Hospital, Xi'an Jiaotong University Medical College, Xi'an, 710068, China.
authors.forename: Bei
authors.initials: B
authors.lastname: Kang
authors.affiliation: Department of Dermatology, The Second Affiliated Hospital, Xi'an Jiaotong University Medical College, Xi'an, 710003, China. weihuizeng2@163.com.
authors.forename: Weihui
authors.initials: W
authors.lastname: Zeng
authors.affiliation: Department of Burn and Plastic Surgery, The Third Affiliated Hospital, Xi'an Jiaotong University Medical College, Xi'an, 710068, China.
authors.forename: Yaowen
authors.initials: Y
authors.lastname: Sun
authors.affiliation: Department of Dermatology, The Third Affiliated Hospital, Xi'an Jiaotong University Medical College, Xi'an, 710068, China.
authors.forename: Fan
authors.initials: F
authors.lastname: Yang
mesh_terms: D017209:Apoptosis; D002478:Cells, Cultured; D017439:Cicatrix, Hypertrophic / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D055513:Connective Tissue Growth Factor / Q000096:biosynthesis* / Q000235:genetics; D005260:Female; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000096:biosynthesis* / Q000235:genetics; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D058570:TOR Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*
chemical_list: C526317:CCN2 protein, human; C542359:MIRN143 microRNA, human; D035683:MicroRNAs; D055513:Connective Tissue Growth Factor; C546842:MTOR protein, human; D051057:Proto-Oncogene Proteins c-akt; D058570:TOR Serine-Threonine Kinases
keywords: Akt/mTOR; Connective tissue growth factor; Hypertrophic scar; MicroRNA