LncRNA MIR503HG promotes hypertrophic scar progression via miR‐143‐3p‐mediated Smad3 expression

Abstract

Hypertrophic scars (HSs) form due to unchecked proliferation of fibrous tissue after an injury to the skin. Recently, lncRNA MIR503HG was shown to be involved in HS. However, the mechanism by which MIR503HG affects the formation and progression of HS still needs further study. qRT-PCR was applied to examine the levels of MIR503HG and miR-143-3p in HS tissues and human hypertrophic scar fibroblasts (hHSFs). The relationships of MIR503HG, miR-143-3p and Smad3 were explored with a dual-luciferase reporter assay. Cell proliferation, apoptosis, and invasion were measured by CCK-8 assay, flow cytometry and transwell assay, respectively. The protein level of Smad3 was tested via Western blotting. MIR503HG was upregulated and miR-143-3p was downregulated in HS versus normal skin tissues. The knockdown of MIR503HG and the overexpression of miR-143-3p suppressed the proliferation and invasion of hHSF, and promoted cell apoptosis. MIR503HG bound to miR-143-3p while miR-143-3p directly targeted Smad3 to inhibit its expression. Suppression of miR-143-3p and overexpression of Smad3, respectively, reversed these effects of knockdown of MIR503HG and overexpression of miR-143-3p on hHSFs. Our research supports a model in which the MIR503HG/miR-143-3p/Smad3 axis serves as a critical regulator of HS, highlighting a promising therapeutic option for HS.

Identifying miRNAs Associated with the Progression of Keloid through mRNA-miRNA Network Analysis and Validating the Targets of miR-29a-3p in Keloid Fibroblasts

“…Wei et al found that miR-143-3p was downregulated in HS compared with normal skin tissue, and the overexpression of miR-143-3p inhibited the proliferation and invasion of HSF and promoted its apoptosis. They also confirmed that miR-143-3p played the above role by directly targeting Smad3 [20].…”

“…Wei et al found that miR-143-3p was downregulated in HS compared with normal skin tissue, and the overexpression of miR-143-3p inhibited the proliferation and invasion of HSF and promoted its apoptosis. They also confirmed that miR-143-3p played the above role by directly targeting Smad3 [ 20 ]. Besides, miR-92a-3p [ 21 ] was also involved in the development of various fibrotic diseases, but the correlation with keloid has not been reported.…”

Corilagin alleviates intestinal ischemia/reperfusion injury by relieving oxidative stress and apoptosis via AMPK/Sirt1-autophagy pathway

“…Activation of AMPK/Sirt1 pathway is reported to restore impaired autophagy and inhibited inflammation reaction and apoptosis in acute pancreatitis, acute kidney injury, diabetic retinopathy and age-related mitochondrial dysfunction. 39 –42 However, the role of AMPK/Sirt1-mediated autophagy is not clearly investigated in II/R. In this study, we found that a decrease in p-AMPK/AMPK and Sirt1 protein expression in II/R rats and CA pretreatment promoted AMPK phosphorylation and Sirt1 expression.…”

Deciphering “Immaturity-Stemness” in Human Epidermal Stem Cells at the Levels of Protein-Coding and Non-Coding Genomes: A Prospective Computational Approach

“…Another candidate lncRNA identified in our study, MIR503HG , has been previously described to be deregulated in tongue squamous cell carcinoma [ 38 ]. Of note, MIR503HG has been also associated with the promotion of pathophysiological processes mediated by dermal fibroblasts, including hypertrophic scar progression [ 39 ], and skin fibrosis, via interaction with TGFB/SMAD signaling [ 40 ].…”