These tools will no longer be maintained as of December 31, 2024. Archived website can be found here. PubMed4Hh GitHub repository can be found here. Contact NLM Customer Service if you have questions.


Pubmed for Handhelds

PUBMED FOR HANDHELDS

Search MEDLINE/PubMed

  • Title: Progranulin alleviates podocyte injury via regulating CAMKK/AMPK-mediated autophagy under diabetic conditions.
    Author: Zhou D, Zhou M, Wang Z, Fu Y, Jia M, Wang X, Liu M, Zhang Y, Sun Y, Zhou Y, Lu Y, Tang W, Yi F.
    Journal: J Mol Med (Berl); 2019 Nov; 97(11):1507-1520. PubMed ID: 31402399.
    Abstract:
    Podocyte injury is considered a major contributor to the development of diabetic nephropathy (DN). Therefore, identification of potential therapeutic targets for preventing podocyte injury has clinical importance. Recent studies have indicated that autophagy is a key homeostatic mechanism to maintaining podocyte integrity and function. 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.
    [Abstract] [Full Text] [Related] [New Search]