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Klotho Regulates ETB Receptor Expression via the PKC/c‐Jun Pathway
Author(s) -
Wang Yuhong,
Sun Zhongjie
Publication year - 2011
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.25.1_supplement.666.5
Subject(s) - klotho , gene knockdown , protein kinase c , hek 293 cells , downregulation and upregulation , receptor , gene silencing , chemistry , transfection , signal transduction , trpc6 , small interfering rna , rottlerin , microbiology and biotechnology , endocrinology , medicine , kidney , biology , gene , transient receptor potential channel , biochemistry
Background Klotho is a newly‐discovered anti‐aging gene. We recently reported that klotho gene delivery prevented progression of spontaneous hypertension and renal damage. In vivo expression of klotho upregulated renal ETB receptors in spontaneous hypertensive rats. The purpose of this study was to determine the molecular mechanism of the regulation of ETB receptors by klotho in HEK 293 cells. Methods & Results Overexpression of klotho was achieved using AAV plasmid carrying the mouse klotho full‐length cDNA (mKL). Silencing of klotho gene was achieved using small interfering RNA (siRNA). Protein expression of ETA and ETB receptors and c‐Jun was measured by western blot. Nitric Oxide (NO) production was evaluated by flowcytometry using the DAF probe. Overexpression of klotho dose‐dependently increased ETB protein expression and NO production in HEK 293 cells. RNAi knockdown of klotho resulted in a selective decrease in mRNA and protein expression of ETB. On the other hand, klotho gene delivery increased PKC activity and enhanced c‐Jun expression. Blockade of PKC activation by a PKC inhibitor bisindolylmaleimide abolished the klotho‐induced increases in ETB and c‐Jun expression in HEK 293 cells. These results suggest that the upregulation of ETB by klotho may be PKC/c‐Jun‐dependent. Conclusions Klotho may regulate ETB expression via the PKC/c‐Jun pathway in HEK 293 cells. This finding may offer new insights into the molecular mechanism of klotho‐mediated renal protection.