Soluble klotho induces the heat shock factor 1 through EGR1 expression

The transcription factor array approach was used to identify novel signaling pathways that are regulated by klotho gene/proteins. Klotho deficiency (kl−/−) largely decreased HSF1 levels and impaired heat shock protein expression. Additionally, klotho transcriptionally regulates HSF1 by modulating EGR-1. AbstractKlotho 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.

Source: BioFactors - April 4, 2024 Category: Biochemistry Authors: Soo ‐A Kim, Nguyen Khanh Toan, Sang‐Gun Ahn Tags: RESEARCH ARTICLE Source Type: research