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
  • 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. [email protected].
  • 7. Department of Endocrinology, The First Affiliated Hospital of Anhui Medical University, Hefei, China. [email protected].
  • # 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.

Products