Protective effect of bone marrow mesenchymal stem cells modified with klotho on renal ischemia-reperfusion injury

Ren Fail. 2019 Nov;41(1):175-182. doi: 10.1080/0886022X.2019.1588131.

Abstract

Objective: To detect the combination protective effect of bone marrow mesenchymal stem cells (BMSCs) and Klotho gene on the renal ischemia-reperfusion injury (RIRI).

Methods: BMSCs isolated from rats were transfected with Klotho gene to form BMSCKl. We injected BMSCKl to allogenic rat RIRI model. After 24 h and 72 h, we detected the serum creatinine (SCr), malondialdehyde (MDA), and superoxide dismutase (SOD) in renal tissue, Hematoxylin-eosin (HE) staining, and TUNEL of renal pathology. The expression of FoxO1 and p-FoxO1 in post-hypoxia tubular epithelial cells of normal rat kidney (NRK-52E) were detected by Western blot after cocultured with BMSCKl.

Results: Comparing with BMSCCon group, Rats in BMSCKl group had lower SCr and MDA but higher SOD. Both HE and TUNEL score of renal tissue in BMSCKl group were lower than that of BMSCCon group. Western blot indicated that FoxO1 was upregulated, while p-FoxO1 was downregulated in post-hypoxia NRK-52E cells.

Conclusions: BMSCs transfected with Klotho gene can further ameliorate RIRI. The possible mechanism may be attributed to the upregulation of SOD in NRK-52E caused by Klotho-FoxO1 axis.

Keywords: FoxO1; Klotho; Renal ischemia-reperfusion injury; bone marrow mesenchymal stem cells; gene transfection.

MeSH terms

  • Animals
  • Cell Engineering / methods
  • Cell Line
  • Coculture Techniques
  • Disease Models, Animal
  • Down-Regulation
  • Glucuronidase / genetics
  • Glucuronidase / metabolism*
  • Humans
  • Kidney / blood supply
  • Kidney / metabolism
  • Kidney / pathology
  • Klotho Proteins
  • Male
  • Mesenchymal Stem Cell Transplantation / methods*
  • Mesenchymal Stem Cells / metabolism*
  • Nerve Tissue Proteins / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Reperfusion Injury / pathology
  • Reperfusion Injury / therapy*
  • Signal Transduction
  • Superoxide Dismutase / metabolism
  • Transfection
  • Treatment Outcome
  • Up-Regulation

Substances

  • Nerve Tissue Proteins
  • Foxo1 protein, rat
  • Superoxide Dismutase
  • Glucuronidase
  • Klotho Proteins

Grants and funding

This work was supported by 1.3.5 Project for Disciplines of Excellence, West China Hospital, Sichuan University [grant no. ZY2016104], and The Affiliated Hospital of Southwest Medical University Academic Project [16012].