Postburn Downregulation of miR-148a-3p and Its Regulatory Mechanism in Hypertrophic Scar Formation

BACKGROUNDBurn injuries represent a common form of trauma, and their healing process poses a significant clinical challenge, frequently complicated by aberrant scarring. Recent studies have found that miR-148a-3p is an important regulator involved in the process of tissue fibrosis, but the specific mechanism of action of miR-148a-3p in burn wound repair still needs to be elucidated.

METHODSClinical data were collected from participants, and serum miR-148a-3p expression was measured by qRT-PCR in both burn patients and healthy controls. ROC curve analysis and logistic regression were employed to evaluate hypertrophic scar occurrence at 6-month follow-up. In vitro, a heat-injured fibroblast model was established. The cellular proliferation, migration, and expression of fibrosis markers (Col I, α-SMA, TGF-β1) were assessed using CCK-8 assay, Transwell migration assay, and qRT-PCR. The targeting relationship between miR-148a-3p and MEOX2 was predicted by bioinformatics analysis and verified by dual-luciferase reporter assay. Functional rescue experiments were performed to confirm the regulatory mechanism.

RESULTSCompared to healthy subjects, miR-148a-3p expression was significantly lower than that of the healthy control group, and the reduction was more pronounced in patients with scarring, regardless of age, weight, or sex. The expression level of miR-148a-3p and the depth of burn injury constitute important risk factors for scarring, which has significant diagnostic value. The expression level of miR-148a-3p in human skin fibroblasts (WS1) decreased significantly after heat treatment compared with that before treatment. Overexpression of miR-148a-3p inhibited the proliferation and migration of WS1 cells and downregulated the expression of fibrosis-related markers such as collagen I, α-SMA, and TGF-β1. Mechanistic studies have shown that miR-148a-3p negatively regulates its expression by directly binding to MEOX2, and overexpression of MEOX2 can reverse the cell function and other disorders caused by miR-148a-3p.

CONCLUSIONmiR-148a-3p plays a key role in postburn hypertrophic scarring by targeting MEOX2 to affect fibroblast activity, suggesting its potential value as a diagnostic marker and a target for scar prevention and treatment.

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