Alterations in the Expression of miR-148a-5p, TGF-β1, and TGF-βR2 in Skin Samples Exposed to Sulfur Mustard

Iran Biomed J. 2025 Sep 1;29(5):344-51. doi: 10.61882/ibj.5198.

Abstract

Background: Sulfur mustard exposure causes chronic cutaneous injuries characterized by inflammation, fibrosis, and delayed wound healing. MiRNAs, such as miR-148a-5p, have been implicated in regulating the TGF-β signaling pathways involved in these processes. This study aimed to evaluate whether alterations in the expression of miR-148a-5p, TGF-β1, and TGF-βR2 are associated with long-term SM-induced skin damage.

Methods: Skin biopsy samples were collected from 20 SM-exposed veterans and 20 healthy controls. Total RNA was extracted, and quantitative real-time PCR was performed to assess the expression levels of miR-148a-5p, TGF-β1, and TGF-βR2. Group differences were analyzed using a t-test, and ROC curves were generated to evaluate diagnostic performance.

Results: Expression levels of miR-148a-5p, TGF-β1, and TGF-βR2 were significantly lower in SM-exposed skin compared with controls (miR-148a-5p: p = 0.0010; TGF-β1: p < 0.0001; TGF-βR2: p < 0.0001). Based on ROC analysis, miR-148a-5p and TGF-βR2 indicated promising discriminative potential, whereas TGF-β1 did not reach statistical significance (AUC = 0.65; p = 0.0877).

Conclusion: Our findings suggest that reduced expression of miR-148a-5p and TGF-βR2 may contribute to SM-related skin injury. Both markers demonstrated potential diagnostic utility and could aid in risk stratification and monitoring in SM-induced skin disease, pending further validation in larger cohorts.

Keywords: Biomarkers; Gene expression; Mustard gas; Skin; Transforming growth factor beta.

MeSH terms

  • Adult
  • Case-Control Studies
  • Chemical Warfare Agents / toxicity
  • Gene Expression Regulation* / drug effects
  • Humans
  • Male
  • MicroRNAs* / genetics
  • MicroRNAs* / metabolism
  • Middle Aged
  • Mustard Gas* / toxicity
  • Receptor, Transforming Growth Factor-beta Type II* / genetics
  • Receptor, Transforming Growth Factor-beta Type II* / metabolism
  • Skin* / drug effects
  • Skin* / metabolism
  • Skin* / pathology
  • Transforming Growth Factor beta1* / genetics
  • Transforming Growth Factor beta1* / metabolism

Substances

  • MicroRNAs
  • Mustard Gas
  • Transforming Growth Factor beta1
  • MIRN148 microRNA, human
  • Receptor, Transforming Growth Factor-beta Type II
  • TGFBR2 protein, human
  • TGFB1 protein, human
  • Chemical Warfare Agents