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

IF 15.8 1区医学 Q1 CELL BIOLOGY

Science Translational Medicine Pub Date : 2024-10-30 DOI:10.1126/scitranslmed.adl5514

Valentina Villani, Camille Nicolas Frank, Paolo Cravedi, Xiaogang Hou, Sofia Bin, Anna Kamitakahara, Cristiani Barbati, Roberta Buono, Stefano Da Sacco, Kevin V. Lemley, Roger E. De Filippo, Silvia Lai, Alessandro Laviano, Valter D. Longo, Laura Perin

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引用次数: 0

Abstract

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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肾脏特异性禁食模拟饮食可诱导荚膜细胞重编程并恢复肾小球病变患者的肾功能。

周期性的模拟禁食（FMD）可以促进小鼠胰腺、血液、内脏和神经系统的再生并减少损伤，但对肾脏疾病的影响尚不清楚。此外，FMD 还未在大鼠身上进行过测试。在这里，我们发现，与未接受饮食干预的肾脏受损动物相比，循环服用新开发的低盐 FMD（LS-FMD）可使嘌呤霉素诱导的肾病大鼠的蛋白尿、肾小球结构和功能恢复正常。LS-FMD 可诱导调节肾脏基因程序，类似于多个肾脏结构中的肾脏发育过程。在大鼠肾损伤模型中，LS-FMD 还能激活荚膜细胞系重编程途径，并促进成熟荚膜细胞的静止状态。在一项针对慢性肾病患者的试验性临床研究中，与未接受 FMD 循环治疗的患者相比，每月 5 天、持续 3 个月的 FMD 循环治疗可促进肾脏保护，包括减少蛋白尿和改善血管内皮功能。这些结果表明，FMD 循环可促进多种肾细胞类型的重编程，并导致大鼠肾小球损伤逆转，因此应在治疗进展性肾病方面进行进一步试验。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Science Translational Medicine CELL BIOLOGY-MEDICINE, RESEARCH & EXPERIMENTAL

CiteScore

26.70

自引率

1.20%

发文量

309

审稿时长

1.7 months

期刊介绍： Science Translational Medicine is an online journal that focuses on publishing research at the intersection of science, engineering, and medicine. The goal of the journal is to promote human health by providing a platform for researchers from various disciplines to communicate their latest advancements in biomedical, translational, and clinical research. The journal aims to address the slow translation of scientific knowledge into effective treatments and health measures. It publishes articles that fill the knowledge gaps between preclinical research and medical applications, with a focus on accelerating the translation of knowledge into new ways of preventing, diagnosing, and treating human diseases. The scope of Science Translational Medicine includes various areas such as cardiovascular disease, immunology/vaccines, metabolism/diabetes/obesity, neuroscience/neurology/psychiatry, cancer, infectious diseases, policy, behavior, bioengineering, chemical genomics/drug discovery, imaging, applied physical sciences, medical nanotechnology, drug delivery, biomarkers, gene therapy/regenerative medicine, toxicology and pharmacokinetics, data mining, cell culture, animal and human studies, medical informatics, and other interdisciplinary approaches to medicine. The target audience of the journal includes researchers and management in academia, government, and the biotechnology and pharmaceutical industries. It is also relevant to physician scientists, regulators, policy makers, investors, business developers, and funding agencies.