Research Paper Volume 15, Issue 3 pp 791—809
Hair follicle mesenchymal stem cell exosomal lncRNA H19 inhibited NLRP3 pyroptosis to promote diabetic mouse skin wound healing
- 1 Department of Cardiology, China-Japan Union Hospital of Jilin University, Changchun 130031, China
- 2 School of Public Health, Beihua University, Jilin 132033, China
- 3 College of Basic Medicine, Beihua University, Jilin 132033, China
- 4 Department of Laboratory Animal Science, China Medical University, Shenyang 110122, China
Received: May 30, 2022 Accepted: February 2, 2023 Published: February 14, 2023
https://doi.org/10.18632/aging.204513How to Cite
Copyright: © 2023 Yang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Abstract
Skin wounds caused by diabetes are a major medical problem. Mesenchymal stem cell-derived exosomes hold promise to quicken wound healing due to their ability to transfer certain molecules to target cells, including mRNAs, microRNAs, lncRNAs, and proteins. Nonetheless, the specific mechanisms underlying this impact are not elucidated. Therefore, this research aimed to investigate the effect of MSC-derived exosomes comprising long non-coding RNA (lncRNA) H19 on diabetic skin wound healing. Hair follicle mesenchymal stem cells (HF-MSCs) were effectively isolated and detected, and exosomes (Exo) were also isolated smoothly. Pretreatment with 30 mM glucose for 24 h (HG) could efficiently induce pyroptosis in HaCaT cells. Exosomal H19 enhanced HaCaT proliferation and migration and inhibited pyroptosis by reversing the stimulation of the NLRP3 inflammasome. Injection of exosomes overexpressing lncRNA H19 to diabetic skin wound promoted sustained skin wound healing, whereas sh-H19 exosomes did not have this effect. In conclusion, Exosomes overexpressing H19 promoted HaCaT proliferation, migration and suppressed pyroptosis both in vitro and in vivo. Therefore, HFMSC-derived exosomes that overexpress H19 may be included in strategies for healing diabetic skin wounds.
Abbreviations
HF-MSCs: Hair follicle mesenchymal stem cells; HF-MSCs-Exo: HF-MSCs derived exosomes; HF-MSCs -CM: HF-MSCs derived conditioned medium; HF-MSCs -dp-Ex: exosomes-deprived HF-MSCs -conditioned media; AIF: apoptosis-inducing factor; cyt C: cytochrome C; HaCaT: immortalized human keratinocytes; MSC: mesenchymal stem cells; GAPDH: Glyceraldehyde-3-phosphate dehydrogenase; PMSF: Phenylmethylsulfonyl fluoride; HRP: Horseradish peroxidase; DMEM: Dulbecco’s modified Eagle medium; FISH: fluorescence in situ hybridization; FBS: Fetal bovine serum; DMSO: Dimethylsulfoxide; H ɮ: hematoxylin and eosin; BSA: bovine serum albumin; NLRP3: Nod-like receptor family pyrin domain comprising 3 mRNA; lncRNAs: Long non-coding RNAs.