A kidney-specific fasting-mimicking diet induces podocyte reprogramming and restores renal function in glomerulopathy

足细胞 肾小球疾病 重编程 肾功能 医学 肾小球 内分泌学 内科学 细胞生物学 生物 肾小球肾炎 蛋白尿 生物化学 细胞
作者
Valentina Villani,Camille Nicolas Frank,Paolo Cravedi,Xiaogang Hou,Sofia Bin,Anna Kamitakahara,Cristiana Barbati,Roberta Buono,Stefano Da Sacco,Kevin V. Lemley,Roger E. De Filippo,Silvia Lai,Alessandro Laviano,Valter D. Longo,Laura Perin
出处
期刊:Science Translational Medicine [American Association for the Advancement of Science (AAAS)]
卷期号:16 (771)
标识
DOI:10.1126/scitranslmed.adl5514
摘要

Cycles of a fasting-mimicking diet (FMD) promote regeneration and reduce damage in the pancreases, blood, guts, and nervous systems of mice, but their effect on kidney disease is unknown. In addition, a FMD has not been tested in rats. Here, we show that cycles of a newly developed low-salt FMD (LS-FMD) restored normal proteinuria and nephron structure and function in rats with puromycin-induced nephrosis compared with that in animals with renal damage that did not receive the dietary intervention. LS-FMD induced modulation of a nephrogenic gene program, resembling renal developmental processes in multiple kidney structures. LS-FMD also activated podocyte-lineage reprogramming pathways and promoted a quiescent state in mature podocytes in the rat kidney damage model. In a pilot clinical study in patients with chronic kidney disease, FMD cycles of 5 days each month for 3 months promoted renoprotection, including reduction of proteinuria and improved endothelial function, compared with that in patients who did not receive the FMD cycles. These results show that FMD cycles, which promote the reprogramming of multiple renal cell types and lead to glomerular damage reversal in rats, should be tested further for the treatment of progressive kidney diseases.
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