Overexpression of klotho protein modulates uninephrectomy-induced compensatory renal hypertrophy by suppressing IGF-I signals

The klotho gene is highly expressed in the distal convoluted tubule of the kidney, while its encoded protein has many physiological and pathophysiological renal roles. We investigated the effect of klotho protein on physiological compensatory renal hypertrophy after nephrectomy in klotho transgenic (KLTG) mice. Renal hypertrophy was suppressed in KLTG mice compared with wild-type mice, and this was associated with suppression of insulin growth factor-1 (IGF-1) signaling by klotho protein. In vitro, IGF-1 signaling was suppressed in human proximal tubular cells transfected with the klotho plasmid. Our data suggest that klotho modulates compensatory renal hypertrophy after nephrectomy via suppression of the IGF-1 signaling pathway, indicating a novel physiological role for klotho protein in the kidney.

► We explored the role of klotho in compensatory renal hypertrophy.
► Klotho protein suppressed glomerular and tubular cell hypertrophy.
► This mechanism was associated with modulation of the IGF-1/mTOR pathway.