Progranulin alleviates podocyte injury via regulating CAMKK/AMPK-mediated autophagy under diabetic conditions

This study was to elucidate the role of progranulin (PGRN), a secreted glycoprotein, in the modulation of podocyte autophagic process and podocyte injury under a diabetic condition. PGRN was downregulated in the kidney from diabetic mice and podocytes under a high-glucose (HG) condition. PGRN deficiency exacerbated the renal dysfunction and glomerular structural alterations. In vitro, treatment with recombinant human PGRN (rPGRN) attenuated HG-induced podocyte injury accompanied by enhanced autophagy. Inhibition of autophagy disturbed the protective effects of PGRN in HG-induced podocytotoxicity. Furthermore, PGRN induced autophagy via the PGRN-CAMKK-AMPK pathway. Collectively, our data identified the protective role of PGRN in podocyte injury via restoring autophagy and activating the CAMKK-AMPK pathway, which may pave the road to new therapeutic modalities for the treatment of diabetic nephropathy.Key messages• PGRN level is reduced in kidney of diabetic mice and high-glucose–treated podocytes.• PGRN deficiency exacerbates renal injury in diabetic mice.• PGRN protects against high-glucose–induced podocyte injury.• PGRN restores high-glucose–inhibited autophagy in podocytes.• CAMKK-AMPK pathway is required for the protective role of PGRN in podocyte injury.
Source: Journal of Molecular Medicine - Category: Molecular Biology Source Type: research