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尿源干细胞分泌的 Klotho 通过抑制 TGF-β 信号通路在 HK-2 纤维化模型中发挥关键作用。

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

机构信息

Institute of Cell Biology and Regenerative Medicine, EHLBIO Co., Ltd., Uiwang-si 16006, Korea.

Department of Medical Biotechnology, Dongguk University, Goyang-si 10326, Korea.

出版信息

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

DOI:10.3390/ijms23095012
PMID:35563402
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9105028/
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.

摘要

肾纤维化是一种不可逆转且进行性的过程，可导致慢性肾脏病 (CKD) 严重功能障碍。CKD 阶段的进展与血清 Klotho 水平逐渐降低高度相关。我们专注于 Klotho 蛋白作为对抗 CKD 的关键治疗因子。尿源干细胞 (UDSC) 因其肾脏组织特异性起源而被确定为肾脏再生和 CKD 治疗的新型干细胞来源。然而，UDSC 和肾脏中的 Klotho 之间的关系尚不清楚。在这项研究中，我们发现 UDSC 是表达 Klotho 蛋白的干细胞，其表达强度强于其他间充质干细胞 (MSC)。UDSC 还通过在体外模型中抑制人肾近端小管细胞 HK-2 中的转化生长因子 (TGF)-β 来抑制纤维化。Klotho siRNA 沉默降低了 UDSC 的 TGF 抑制能力。在这里，我们提出了一种替代细胞来源，通过 UDSC 的起源特异性和 Klotho 的抗纤维化作用的协同效应，可以克服 MSC 的局限性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ed93/9105028/2f45a7f75450/ijms-23-05012-g006a.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ed93/9105028/2f45a7f75450/ijms-23-05012-g006a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ed93/9105028/64261e5d9441/ijms-23-05012-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ed93/9105028/8a8b083dc9ff/ijms-23-05012-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ed93/9105028/85787de2a4b6/ijms-23-05012-g003.jpg
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