Soluble klotho induces the heat shock factor 1 through EGR1 expression

IF 5 3区生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

BioFactors Pub Date : 2024-04-04 DOI:10.1002/biof.2056

Soo‐A Kim, Nguyen Khanh Toan, Sang‐Gun Ahn

引用次数: 0

Abstract

Klotho is an antiaging protein that has multiple functions. The purpose of this study is to investigate whether soluble klotho plays a role in cellular stress response pathways. We found that klotho deficiency (kl−/−) largely decreased HSF1 levels and impaired heat shock protein expression. Interestingly, recombinant soluble klotho‐induced HSF1 and HSPs such as HSP90, HSP70, and HSP27 in kl−/− mouse embryonic fibroblasts (MEFs). Soluble Klotho treatment also induced cell proliferation and HSF1 promoter activity in MEF kl−/− cells in a concentration‐dependent manner. Furthermore, using point mutagenesis, we identified regulatory/binding sites of transcription factors EGR1 regulated by soluble klotho in the HSF1 promoter. Taken together, our findings unravel the molecular basis of klotho and provide molecular evidence supporting a direct interaction between soluble klotho and HSF1‐mediated stress response pathway.

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可溶性 klotho 通过 EGR1 的表达诱导热休克因子 1

Klotho 是一种抗衰老蛋白，具有多种功能。本研究旨在探讨可溶性klotho是否在细胞应激反应途径中发挥作用。我们发现，Klotho缺乏症（kl-/-）在很大程度上降低了HSF1的水平，并损害了热休克蛋白的表达。有趣的是，重组可溶性 Klotho 能诱导 kl-/- 小鼠胚胎成纤维细胞（MEFs）中的 HSF1 和 HSPs，如 HSP90、HSP70 和 HSP27。可溶性 Klotho 还能以浓度依赖的方式诱导 MEF kl-/- 细胞的细胞增殖和 HSF1 启动子活性。此外，通过点突变，我们确定了 HSF1 启动子中受可溶性 Klotho 调控的转录因子 EGR1 的调控/结合位点。总之，我们的研究结果揭示了klotho的分子基础，并提供了分子证据支持可溶性klotho与HSF1介导的应激反应途径之间的直接相互作用。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

BioFactors 生物-内分泌学与代谢

CiteScore

11.50

自引率

3.30%

发文量

审稿时长

6-12 weeks

期刊介绍： BioFactors, a journal of the International Union of Biochemistry and Molecular Biology, is devoted to the rapid publication of highly significant original research articles and reviews in experimental biology in health and disease. The word “biofactors” refers to the many compounds that regulate biological functions. Biological factors comprise many molecules produced or modified by living organisms, and present in many essential systems like the blood, the nervous or immunological systems. A non-exhaustive list of biological factors includes neurotransmitters, cytokines, chemokines, hormones, coagulation factors, transcription factors, signaling molecules, receptor ligands and many more. In the group of biofactors we can accommodate several classical molecules not synthetized in the body such as vitamins, micronutrients or essential trace elements. In keeping with this unified view of biochemistry, BioFactors publishes research dealing with the identification of new substances and the elucidation of their functions at the biophysical, biochemical, cellular and human level as well as studies revealing novel functions of already known biofactors. The journal encourages the submission of studies that use biochemistry, biophysics, cell and molecular biology and/or cell signaling approaches.

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