Aberrant miR-21 and miR-200b expression and its pro-fibrotic potential in hypertrophic scars.
The post-traumatic hypertrophic scar (HS) is a fibrotic disease with excessive extracellular matrix (ECM) production by fibroblasts in response to tissue injury. Although dysregulation of miRNAs is known to be involved in a variety of pathophysiologic processes, the role of miRNA in hypertrophic scar formation is unclear. Abnormal expression of miRNA in fibrosis has been investigated in several studies. The transforming growth factor β1 (TGF-β1) promotes fibroblasts proliferation, the synthesis of collagen and other extracellular matrix, and ultimately leads to the formation of the HS by inducing excessive deposition of ECM. We identified two miRNAs whose expression was correlated with fibrotic diseases: miR-21 and miR-200b. This study further confirmed that after stimulation with TGF-β1, the expression of miR-21 was increased, whereas the mRNA level of SMAD7 was decreased in fibroblasts. TGF-β1 reduced the expression of miR-200b, while it augmented that of Zinc finger E-box-binding homeobox 1(Zeb1). Our experiments demonstrated that the expression of miR-21 and miR-200b are related to a disorder, and the TGF-β/miR-21/Smad7 and TGF-β/miR200b/Zeb1 pathways might participate in the pathogenesis of HS. Thus, a novel, beyond the traditional methods, approach for HS treatment via miRNA therapeutics could have been provided.
Department of Plastic and Reconstructive Surgery, Shanghai 9th People's Hospital, Shanghai Jiao Tong University School of Medicine, 639 Zhi Zao Ju Road, Shanghai 200011, China.
Renpeng
R
Zhou
Department of Burn and Plastic Surgery, People's Hospital of Dancheng County, 42 Ren Min Road, Zhoukou City, Henan Province 477150, China.
Qi
Q
Zhang
Institute of Arthritis Research, Shanghai Academy of Chinese Medical Sciences and Guanghua Integrative Medicine Hospital, China.
Yun
Y
Zhang
Department of Plastic and Reconstructive Surgery, Shanghai 9th People's Hospital, Shanghai Jiao Tong University School of Medicine, 639 Zhi Zao Ju Road, Shanghai 200011, China.
Shibo
S
Fu
Department of Plastic and Reconstructive Surgery, Shanghai 9th People's Hospital, Shanghai Jiao Tong University School of Medicine, 639 Zhi Zao Ju Road, Shanghai 200011, China. Electronic address: wangchen2369@163.com.
Chen
C
Wang
D000293:Adolescent; D000328:Adult; D002478:Cells, Cultured; D002648:Child; D002675:Child, Preschool; D017439:Cicatrix, Hypertrophic / Q000235:genetics* / Q000473:pathology; D005260:Female; D005355:Fibrosis / Q000235:genetics* / Q000473:pathology; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000235:genetics*; D053773:Transforming Growth Factor beta1 / Q000378:metabolism; D055815:Young Adult
C533896:MIRN200 microRNA, human; C524940:MIRN21 microRNA, human; D035683:MicroRNAs; D053773:Transforming Growth Factor beta1
Fibrosis; Hypertrophic scar; TGF -β1; miR-200b; miR-21