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

Overview

Journal Int J Mol Sci

Publisher MDPI

Specialties Biochemistry
Chemistry
Molecular Biology

Date 2022 May 14

PMID 35563402

Authors

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

Affiliations

Soon will be listed here.

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.

Citing Articles

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In vivo safety and biodistribution profile of Klotho-enhanced human urine-derived stem cells for clinical application.

Kim S, Lee S, Jin J, So H, Lee J, Ji M Stem Cell Res Ther. 2023; 14(1):355.

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