2. Academic Validation
  3. MicroRNA-221-3p inhibits the inflammatory response of keratinocytes by regulating the DYRK1A/STAT3 signaling pathway to promote wound healing in diabetes

MicroRNA-221-3p inhibits the inflammatory response of keratinocytes by regulating the DYRK1A/STAT3 signaling pathway to promote wound healing in diabetes

  • Commun Biol. 2024 Mar 9;7(1):300. doi: 10.1038/s42003-024-05986-0.
Keyan Hu # 1 2,  Lei Liu # 1,  Songtao Tang # 1,  Xin Zhang 1,  Hongfeng Chang 1,  Wenyang Chen 3,  Taotao Fan 4,  Lesha Zhang 5,  Bing Shen 6,  Qiu Zhang 7
Affiliations

Affiliations

  • 1 Department of Endocrinology, The First Affiliated Hospital of Anhui Medical University, Hefei, China.
  • 2 Department of Endocrinology, The First Affiliated Hospital, and College of Clinical Medicine of Henan University of Science and Technology, Luoyang, China.
  • 3 Central Laboratory, Fujian Medical University Union Hospital, Fuzhou, China.
  • 4 Center of Experimental Practice, Anhui Medical University, Hefei, China.
  • 5 School of Basic Medical Sciences, Anhui Medical University, Hefei, People's Republic of China.
  • 6 Dr. Neher's Biophysics Laboratory for Innovative Drug Discovery, State Key Laboratory of Quality Research in Chinese Medicine, Macau University of Science and Technology, Macau, China. bshen@must.edu.mo.
  • 7 Department of Endocrinology, The First Affiliated Hospital of Anhui Medical University, Hefei, China. zhangqiu@ahmu.edu.cn.
  • # Contributed equally.
PMID: 38461326 DOI: 10.1038/s42003-024-05986-0
Abstract

Diabetic foot ulcer (DFU), a serious complication of diabetes, remains a clinical challenge. MicroRNAs affect inflammation and may have therapeutic value in DFU. Here, we find that an miR-221-3p mimic reduces the inflammatory response and increases skin wound healing rates in a mouse model of diabetes, whereas miR-221-3p knockout produced the opposite result. In human keratinocytes cells, miR-221-3p suppresses the inflammatory response induced by high glucose. The gene encoding DYRK1A is a target of miR-221-3p. High glucose increases the expression of DYRK1A, but silencing DYRK1A expression decreases high glucose-induced inflammatory cytokine release via dephosphorylation of STAT3, a substrate of DYRK1A. Application of miR-221-3p mimic to human keratinocytes cells not only decreases DYRK1A expression but also inhibits high glucose-induced production of inflammatory cytokines to promote wound healing. This molecular mechanism whereby miR-221-3p regulates inflammation through the DYRK1A/STAT3 signaling pathway suggests targets and therapeutic approaches for treating DFU.

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