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Updated: Jun 29, 2025

Measurements of Physiological Stress Responses in C. Elegans
Published on: May 21, 2020
Soluble klotho induces the heat shock factor 1 through EGR1 expression
Soo-A Kim1, Nguyen Khanh Toan2, Sang-Gun Ahn2
1Department of Biochemistry, School of Oriental Medicine, Dongguk University, Gyeongju, Republic of Korea.
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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