2. Academic Validation
  3. Rab37 Promotes Endothelial Differentiation and Accelerates ADSC-Mediated Diabetic Wound Healing through Regulating Secretion of Hsp90α and TIMP1

Rab37 Promotes Endothelial Differentiation and Accelerates ADSC-Mediated Diabetic Wound Healing through Regulating Secretion of Hsp90α and TIMP1

  • Stem Cell Rev Rep. 2023 Jan 11. doi: 10.1007/s12015-022-10491-0.
Haili Huang 1,  Ling Liang 1,  Dan Sun 1,  Jin Li 1,  Wentao Wang 1,  Lixia Zha 1,  Jiaqi Yang 1,  Kunyan Pan 1,  Xianmou Fan 1,  Chengzhang He 1,  Xudong Tang 2,  Peihua Zhang 3
Affiliations

Affiliations

  • 1 Department of Plastic Surgery, Affiliated Hospital of Guangdong Medical University, No. 57 Renmin Avenue South, Xiashan District, Zhanjiang City, 524001, Guangdong Province, China.
  • 2 Institute of Biochemistry and Molecular Biology, Collaborative Innovation Center for Antitumor Active Substance Research and development, Guangdong Medical University, Zhanjiang, China.
  • 3 Department of Plastic Surgery, Affiliated Hospital of Guangdong Medical University, No. 57 Renmin Avenue South, Xiashan District, Zhanjiang City, 524001, Guangdong Province, China. zhangph@gdmu.edu.cn.
PMID: 36627432 DOI: 10.1007/s12015-022-10491-0
Abstract

Accumulating evidence indicates that adipose tissue-derived mesenchymal stem cells (ADSCs) are an effective treatment for diabetic refractory wounds. However, the application of ADSCs to diabetic wounds is still limited, indicating that we still lack sufficient knowledge regarding regulators/mediators of ADSCs during wound healing. Rab37, a member of RabGTPase, may function as regulator of vesicle trafficking, which is a crucial event for the secretion of cytokines by ADSCs. Our previous study indicated that Rab37 promotes the adiopogenic differentiation of ADSCs. In this study, we explored the role of Rab37 in ADSC-mediated diabetic wound healing. An in vivo study in db/db diabetic mice showed that Rab37-expressing ADSCs shortened the wound closure time, improved re-epithelialization and collagen deposition, and promoted angiogenesis during wound healing. An in vitro study showed that Rab37 promoted the proliferation, migration and endothelial differentiation of ADSCs. LC-MS/MS analysis identified Hsp90α and TIMP1 as up-regulated cytokines in conditioned media of Rab37-ADSCs. The up-regulation of Rab37 enhanced the secretion of Hsp90α and TIMP1 during endothelial differentiation and under high-glucose exposure. Interestingly, Rab37 promoted the expression of TIMP1, but not Hsp90α, during endothelial differentiation. PLA showed that Rab37 can directly bind to Hsp90α orTIMP1 in ADSCs. Moreover, Hsp90α and TIMP1 knockdown compromised the promoting effects of Rab37 on the proliferation, migration and endothelial differentiation of ADSCs. In conclusion, Rab37 promotes the proliferation, migration and endothelial differentiation of ADSCs and accelerates ADSC-mediated diabetic wound healing through regulating the secretion of Hsp90α and TIMP1.

Keywords

Adipose-tissue-derived mesenchymal stem cells; Chronic refractory wound; Diabetes; Endothelial differentiation; Hsp90; Rab37.

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