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

Sang Heon Kim, Jeong Ah Jin, Hyung Joon So, Sung Hoon Lee, Tae Wook Kang, Jae Ung Lee, Dae Eun Choi, Jin Young Jeong, Yoon Kyung Chang, Hyunsu Choi, Youngjun Lee, Young Kwon Seo, Hong Ki Lee

Research output: Contribution to journalArticlepeer-review

8 Scopus citations

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 antifibrotic effect of Klotho.

Original languageEnglish
Article number5012
JournalInternational Journal of Molecular Sciences
Volume23
Issue number9
DOIs
StatePublished - 1 May 2022

Keywords

  • chronic kidney disease
  • klotho
  • mesenchymal stem cells
  • renal fibrosis
  • urine-derived stem cells

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