RAB37 Promotes Adipogenic Differentiation of hADSCs via the TIMP1/CD63/Integrin Signaling Pathway

The adipogenic differentiation ability of human adipose-derived mesenchymal stem cells (hADSCs) is critical for the construction of tissue engineering adipose, which shows promising applications in plastic surgery and regenerative medicine. RAB37 is a member of the small RabGTPase family and plays a...

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Main Authors: Haili Huang, Anran Li, Jin Li, Dan Sun, Ling Liang, Kunyan Pan, Chengzhang He, Peihua Zhang
Format: Article
Language:English
Published: Wiley 2021-01-01
Series:Stem Cells International
Online Access:http://dx.doi.org/10.1155/2021/8297063
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author Haili Huang
Anran Li
Jin Li
Dan Sun
Ling Liang
Kunyan Pan
Chengzhang He
Peihua Zhang
author_facet Haili Huang
Anran Li
Jin Li
Dan Sun
Ling Liang
Kunyan Pan
Chengzhang He
Peihua Zhang
author_sort Haili Huang
collection DOAJ
description The adipogenic differentiation ability of human adipose-derived mesenchymal stem cells (hADSCs) is critical for the construction of tissue engineering adipose, which shows promising applications in plastic surgery and regenerative medicine. RAB37 is a member of the small RabGTPase family and plays a critical role in vesicle trafficking. However, the role of RAB37 in adipogenic differentiation of hADSCs remains unclear. Here, we report that both the mRNA and protein levels of RAB37 fluctuated during adipogenic differentiation. Upregulation of RAB37 was observed at the early stage of adipogenic differentiation, which was accompanied by increased expression of transcription factors PPARγ2 and C/EBPα, and lipoprotein lipase (LPL). Overexpression of RAB37 promoted adipogenesis of hADSCs, as revealed by Oil Red O staining and increased expression of PPARγ2, C/EBPα, and LPL. Several upregulated cytokines related to RAB37-mediated adipogenic differentiation were identified using a cytokine array, including tissue inhibitor of matrix metalloproteinase 1 (TIMP1). ELISA confirmed that upregulation of RAB37 increased the secretion of TIMP1 by hADSCs. Proximity ligation assay showed that RAB37 interacts with TIMP1 directly. Knockdown of TIMP1 compromised RAB37-mediated adipogenic differentiation. In addition, TIMP1 binds membrane receptor CD63 and integrin β1. RAB37 promotes Tyr397 phosphorylation of FAK, an important protein kinase of the integrin β1 signaling. Moreover, both knockdown of CD63 and inhibitor of FAK impeded RAB37-mediated adipogenic differentiation. In conclusion, RAB37 positively regulates adipogenic differentiation of hADSCs via the TIMP1/CD63/integrin β1 signaling pathway.
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spelling doaj-art-0d74fa310a1848d68774aa0fb030bcef2025-08-20T03:54:24ZengWileyStem Cells International1687-96782021-01-01202110.1155/2021/8297063RAB37 Promotes Adipogenic Differentiation of hADSCs via the TIMP1/CD63/Integrin Signaling PathwayHaili Huang0Anran Li1Jin Li2Dan Sun3Ling Liang4Kunyan Pan5Chengzhang He6Peihua Zhang7Department of Plastic SurgeryDepartment of Plastic SurgeryDepartment of Plastic SurgeryDepartment of Plastic SurgeryDepartment of Plastic SurgeryDepartment of Plastic SurgeryDepartment of Plastic SurgeryDepartment of Plastic SurgeryThe adipogenic differentiation ability of human adipose-derived mesenchymal stem cells (hADSCs) is critical for the construction of tissue engineering adipose, which shows promising applications in plastic surgery and regenerative medicine. RAB37 is a member of the small RabGTPase family and plays a critical role in vesicle trafficking. However, the role of RAB37 in adipogenic differentiation of hADSCs remains unclear. Here, we report that both the mRNA and protein levels of RAB37 fluctuated during adipogenic differentiation. Upregulation of RAB37 was observed at the early stage of adipogenic differentiation, which was accompanied by increased expression of transcription factors PPARγ2 and C/EBPα, and lipoprotein lipase (LPL). Overexpression of RAB37 promoted adipogenesis of hADSCs, as revealed by Oil Red O staining and increased expression of PPARγ2, C/EBPα, and LPL. Several upregulated cytokines related to RAB37-mediated adipogenic differentiation were identified using a cytokine array, including tissue inhibitor of matrix metalloproteinase 1 (TIMP1). ELISA confirmed that upregulation of RAB37 increased the secretion of TIMP1 by hADSCs. Proximity ligation assay showed that RAB37 interacts with TIMP1 directly. Knockdown of TIMP1 compromised RAB37-mediated adipogenic differentiation. In addition, TIMP1 binds membrane receptor CD63 and integrin β1. RAB37 promotes Tyr397 phosphorylation of FAK, an important protein kinase of the integrin β1 signaling. Moreover, both knockdown of CD63 and inhibitor of FAK impeded RAB37-mediated adipogenic differentiation. In conclusion, RAB37 positively regulates adipogenic differentiation of hADSCs via the TIMP1/CD63/integrin β1 signaling pathway.http://dx.doi.org/10.1155/2021/8297063
spellingShingle Haili Huang
Anran Li
Jin Li
Dan Sun
Ling Liang
Kunyan Pan
Chengzhang He
Peihua Zhang
RAB37 Promotes Adipogenic Differentiation of hADSCs via the TIMP1/CD63/Integrin Signaling Pathway
Stem Cells International
title RAB37 Promotes Adipogenic Differentiation of hADSCs via the TIMP1/CD63/Integrin Signaling Pathway
title_full RAB37 Promotes Adipogenic Differentiation of hADSCs via the TIMP1/CD63/Integrin Signaling Pathway
title_fullStr RAB37 Promotes Adipogenic Differentiation of hADSCs via the TIMP1/CD63/Integrin Signaling Pathway
title_full_unstemmed RAB37 Promotes Adipogenic Differentiation of hADSCs via the TIMP1/CD63/Integrin Signaling Pathway
title_short RAB37 Promotes Adipogenic Differentiation of hADSCs via the TIMP1/CD63/Integrin Signaling Pathway
title_sort rab37 promotes adipogenic differentiation of hadscs via the timp1 cd63 integrin signaling pathway
url http://dx.doi.org/10.1155/2021/8297063
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