title: Resveratrol attenuates senescence of adipose-derived mesenchymal stem cells and restores their paracrine effects on promoting insulin secretion of INS-1 cells through Pim-1.
abstract: OBJECTIVE
  The paracrine effects of mesenchymal stem cells (MSCs) were weakened during aging. This study explored whether resveratrol can attenuate senescence of adipose-derived MSCs (ADMSCs) and whether Pim-1 is involved in resveratrol's effect on paracrine of ADMSCs and insulin secretion of INS-1 cells.
  
  
  METHODS
  CCK-8 assay and SA-b-gal assay were performed to test the protective effect of resveratrol on senescent models. QRT-PCR and western blot analysis were performed to analyze of senescence- and β-cell associated genes. QRT-PCR and ELISA analysis was performed to test telomere length and activity. Immunofluorescence and ELISA assay were performed to assess the paracrine effects on promoting insulin secretion of INS-1 cells.
  
  
  RESULTS
  Resveratrol could protect ADMSCs from H2O2 and D-glucose-induced senescence and also attenuate senescence in long-term cultured ADMSCs in vitro. In addition, resveratrol attenuated H2O2 induced higher expression of senescence-associated genes, including P53, P21, Cyclin D1, IL-6 and MMP1, but increased the expression of Sirt1, a well-known anti-senescence gene. Resveratrol significantly enhanced Pim-1 expression in aging ADMSCs through PI3K/AKT signal pathway. The conditioned medium (CM) of ADMSCs enhanced insulin secretion and expression of the key genes for β-cell function including TFAM, PDX1, GLUT2 and HNF-1α via Pim-1. INS-1 cells with Pim-1 knockdown had decreased insulin secretion.
  
  
  CONCLUSIONS
  This study firstly reported that resveratrol has a protective effect on senescence of ADMSCs and can preserve the paracrine effect of the ADMSCs on promoting insulin secretion of INS-1 cells via Pim-1. Therefore, it might be a promising adjuvant agent for future MSCs based therapy.
authors.affiliation: Department of Endocrinology, Zhengzhou Central Hospital Affiliated to Zhengzhou University, Zhengzhou, China. yanlizhaoo@sina.com.
authors.forename: L-T
authors.initials: LT
authors.lastname: Lei
authors.forename: J-B
authors.initials: JB
authors.lastname: Chen
authors.forename: Y-L
authors.initials: YL
authors.lastname: Zhao
authors.forename: S-P
authors.initials: SP
authors.lastname: Yang
authors.forename: L
authors.initials: L
authors.lastname: He
mesh_terms: D000375:Aging; D000818:Animals; D005947:Glucose / Q000494:pharmacology; D007328:Insulin / Q000494:pharmacology*; D059630:Mesenchymal Stem Cells / Q000187:drug effects*; D051573:Proto-Oncogene Proteins c-pim-1 / Q000378:metabolism*; D051381:Rats; D000077185:Resveratrol; D013267:Stilbenes / Q000494:pharmacology*; D014162:Transfection
chemical_list: D007328:Insulin; D013267:Stilbenes; D051573:Proto-Oncogene Proteins c-pim-1; D005947:Glucose; D000077185:Resveratrol