Aberrant miR-21 and miR-200b expression and its pro-fibrotic potential in hypertrophic scars

Journal Article · Thu Dec 10 04:00:00 EST 2015 · Experimental Cell Research

DOI:https://doi.org/10.1016/J.YEXCR.2015.10.018· OSTI ID:22746389

Zhou, Renpeng ^[1]; Zhang, Qi ^[2]; Zhang, Yun ^[3]; Fu, Shibo ^[1]; Wang, Chen ^[1]

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1. 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)
2. Department of Burn and Plastic Surgery, People's Hospital of Dancheng County, 42 Ren Min Road, Zhoukou City, Henan Province 477150 (China)
3. Institute of Arthritis Research, Shanghai Academy of Chinese Medical Sciences and Guanghua Integrative Medicine Hospital (China)

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. - Highlights: • HS tissue had increased expression of miR-21 and decreased expression of Smad7, lower expression of miR-200b and higher expression of Zeb1. • TGF-β1 downregulated Smad7, which was correlated with the upregulation of miR-21. • TGF-β1 upregulated Zeb1, which was correlated with the downregulation of miR-200b. • miR-200b decreased the expression of Col1A1,Col3A1, Fn, and α-SMA, as well as that of the target Zeb1. • The miR-21 inhibitor decreased expression of Col1A1, Col3A1, Fn, and α-SMA and increased the expression of Smad7.

• OSTI ID: 22746389
• Journal Information: Experimental Cell Research, Journal Name: Experimental Cell Research Journal Issue: 2 Vol. 339; ISSN 0014-4827; ISSN ECREAL
• Country of Publication: United States
• Language: English

Related Subjects

60 APPLIED LIFE SCIENCES
ANIMAL TISSUES
CELL PROLIFERATION
COLLAGEN
FIBROBLASTS
FIBROSIS
GROWTH FACTORS
INJURIES
MESSENGER-RNA
PATHOGENESIS
STIMULATION
SYNTHESIS
ZINC