Mesenchymal stem cells pretreated with melatonin ameliorate kidney functions in a rat model of diabetic nephropathy

Biochem Cell Biol. 2018 Oct;96(5):564-571. doi: 10.1139/bcb-2017-0230. Epub 2018 Feb 9.

Abstract

The aim of this study was to investigate the effect of a regenerative therapy comprising mesenchymal stem cells (MSCs) pretreated with melatonin (MT) as a new therapy for underlying diabetic nephropathy (DN) pathogenesis in a rat model, and its possible effect on autophagy protein Beclin-1. Forty adult male albino Wistar rats were distributed among 4 groups: (i) control, (ii) DN, (iii) MSC-treated, and (iv) treated with MSCs that were pre-incubated in-vitro with MT (5 μmol·L-1 for 24 h; MSCs + MT). MSCs treatment significantly improved the renal functions and ameliorated the measured underlying DN pathogenesis and elevation of Beclin-1 protein levels compared with the DN group. In-vitro pretreatment of MSCs with MT enhanced proliferation and efficiency, and thus improved the kidney functions by increasing superoxide dismutase (SOD-1) and Beclin-1, and decreasing transforming growth factor (TGF-β) markers in the kidney tissue, compared with the MSC group (P < 0.05). In conclusion: MSCs represent a promising target in DN management, and their effect can be intensified by pretreatment with MT. The elevated levels of Beclin-1 could be a mediator.

Keywords: Beclin-1; CSM; MSCs; diabetic nephropathy; melatonin; mélatonine; néphropathie diabétique.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Allografts
  • Animals
  • Diabetic Nephropathies / metabolism
  • Diabetic Nephropathies / pathology
  • Diabetic Nephropathies / therapy*
  • Disease Models, Animal
  • Kidney / metabolism*
  • Kidney / pathology
  • Male
  • Melatonin / pharmacology*
  • Mesenchymal Stem Cell Transplantation*
  • Mesenchymal Stem Cells / metabolism*
  • Mesenchymal Stem Cells / pathology
  • Rats
  • Rats, Wistar

Substances

  • Melatonin