Urine-Derived Stem Cell-Secreted Klotho Plays a Crucial Role in the HK-2 Fibrosis Model by Inhibiting the TGF-β Signaling Pathway

Int J Mol Sci. 2022 Apr 30;23(9):5012. doi: 10.3390/ijms23095012.

Abstract

Renal fibrosis is an irreversible and progressive process that causes severe dysfunction in chronic kidney disease (CKD). The progression of CKD stages is highly associated with a gradual reduction in serum Klotho levels. We focused on Klotho protein as a key therapeutic factor against CKD. Urine-derived stem cells (UDSCs) have been identified as a novel stem cell source for kidney regeneration and CKD treatment because of their kidney tissue-specific origin. However, the relationship between UDSCs and Klotho in the kidneys is not yet known. In this study, we discovered that UDSCs were stem cells that expressed Klotho protein more strongly than other mesenchymal stem cells (MSCs). UDSCs also suppressed fibrosis by inhibiting transforming growth factor (TGF)-β in HK-2 human renal proximal tubule cells in an in vitro model. Klotho siRNA silencing reduced the TGF-inhibiting ability of UDSCs. Here, we suggest an alternative cell source that can overcome the limitations of MSCs through the synergetic effect of the origin specificity of UDSCs and the anti-fibrotic effect of Klotho.

Keywords: chronic kidney disease; klotho; mesenchymal stem cells; renal fibrosis; urine-derived stem cells.

MeSH terms

  • Female
  • Fibrosis
  • Glucuronidase / metabolism
  • Humans
  • Kidney* / metabolism
  • Kidney* / pathology
  • Klotho Proteins*
  • Male
  • Regeneration
  • Renal Insufficiency, Chronic* / metabolism
  • Signal Transduction
  • Stem Cells* / metabolism
  • Transforming Growth Factor beta / metabolism
  • Transforming Growth Factor beta1 / metabolism
  • Urine

Substances

  • Transforming Growth Factor beta
  • Transforming Growth Factor beta1
  • Glucuronidase
  • Klotho Proteins

Grants and funding

This research received no external funding.