2. Academic Validation
  3. Novel microRNA seq-14465_x69 promotes scarless wound healing by targeting TGF-β/SMADs pathway in keratinocytes

Novel microRNA seq-14465_x69 promotes scarless wound healing by targeting TGF-β/SMADs pathway in keratinocytes

  • Cell Signal. 2025 Nov:135:112060. doi: 10.1016/j.cellsig.2025.112060.
Feng Zhao 1,  Jie Fu 2,  Xiaohang Li 3,  Hongxin Lang 4
Affiliations

Affiliations

  • 1 Department of Stem Cells and Regenerative Medicine, Shenyang Key Laboratory of Stem Cell and Regenerative Medicine, China Medical University, Shenyang City, Liaoning Province 110122, China.
  • 2 Medical Cosmetology Department, Qinhuangdao Hospital of Traditional Chinese Medicine, Qinhuangdao City, Hebei Province 066000, China.
  • 3 Department of Hepatobiliary Surgery, The First Hospital of China Medical University, Shenyang City, Liaoning Province 110001, China. Electronic address: lixiaohang@cmu.edu.cn.
  • 4 Department of Stem Cells and Regenerative Medicine, Shenyang Key Laboratory of Stem Cell and Regenerative Medicine, China Medical University, Shenyang City, Liaoning Province 110122, China. Electronic address: hxlang@cmu.edu.cn.
PMID: 40789493 DOI: 10.1016/j.cellsig.2025.112060
Abstract

Fetal skin in early to mid gestation exhibits scar-free wound healing, however, it loses the regenerative capacity in late gestation and adulthood, where fibrosis predominates. Human keratinocytes (hKCs) and human fibroblasts (hFBs) play critical roles in this process, with early- to mid- gestational hKCs enhancing hFB proliferation and migration. MicroRNAs (miRNAs) regulate wound healing, but their roles in scarless repair remains incompletely disclosed. We isolated hKCs from mid- (22-23 weeks) and late- gestational (33-36 weeks) fetal skin and performed miRNA Sequencing (miRNA-seq), identifying seq-14465_x69 as a novel miRNA highly expressed in mid gestation. Bioinformatics and dual-luciferase reporter assays predicted and validated its targeting of TGF-β/SMADs pathway genes. Functional assays including cell proliferation, migration, and a murine full-thickness wound model determined its effects on proliferation, migration, and fibrosis during wound healing. Seq-14465_x69 suppressed TGF-β2, TGF-βR2, and SMAD3, enhanced hFBs migration while reducing Collagen I deposition, and drove accelerated wound closure. Our study revealed seq-14465_x69 as a key miRNA promoting scarless healing by modulating TGF-β/SMADs signaling and extracellular matrix (ECM) remodeling, offering a potential therapeutic target for anti-fibrotic wound management.

Keywords

Scarless healing; Skin wound; miRNA seq-14465_x69.

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