Podocytes in health and disease: from development to regeneration.

IF 3.1 3区生物学 Q3 CELL BIOLOGY

Human Cell Pub Date : 2025-10-02 DOI:10.1007/s13577-025-01296-7

Yusuke Nishimura

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引用次数: 0

Abstract

Podocytes are highly specialized epithelial cells that are essential for maintaining the glomerular filtration barrier. They originate from the metanephric mesenchyme during kidney development, with differentiation tightly regulated by transcription factors, such as Wt1, MafB, and Lmx1b, as well as signaling pathways, including Wnt and Notch. Mature podocytes form intricate foot processes and slit diaphragms, coordinating membrane proteins, such as nephrin and podocin, with the actin cytoskeleton to ensure selective filtration. Owing to their limited regenerative capacity, podocyte injury caused by genetic mutations, mechanical stress, metabolic disorders, or inflammation leads to proteinuria, glomerulosclerosis, and the progression of chronic kidney disease. Recent studies have elucidated diverse injury mechanisms, including apoptosis, necroptosis, ferroptosis, and cytoskeletal dysregulation, highlighting aging and lipid metabolism as key modulators of podocyte vulnerability. Advances in stem cell technology and kidney organoids have enabled the modeling of podocyte development and disease, paving the way for regenerative strategies. This review provides a comprehensive overview of podocyte biology, injury mechanisms, and emerging therapeutic approaches, emphasizing translational opportunities for protecting and restoring podocyte function in kidney diseases.

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足细胞在健康和疾病：从发育到再生。

足细胞是高度特化的上皮细胞，对维持肾小球滤过屏障至关重要。它们起源于肾脏发育过程中的后肾间质，其分化受到转录因子如Wt1、MafB和Lmx1b以及信号通路如Wnt和Notch的严格调控。成熟的足细胞形成复杂的足突和狭缝隔膜，协调膜蛋白，如nephrin和podocin，与肌动蛋白细胞骨架，以确保选择性过滤。由于足细胞的再生能力有限，由基因突变、机械应力、代谢紊乱或炎症引起的足细胞损伤可导致蛋白尿、肾小球硬化和慢性肾病的进展。最近的研究已经阐明了多种损伤机制，包括细胞凋亡、坏死下垂、铁下垂和细胞骨骼失调，并强调衰老和脂质代谢是足细胞易损性的关键调节因子。干细胞技术和肾类器官的进步使足细胞发育和疾病的建模成为可能，为再生策略铺平了道路。本文综述了足细胞生物学、损伤机制和新兴的治疗方法，强调了在肾脏疾病中保护和恢复足细胞功能的转化机会。

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

Human Cell CELL BIOLOGY-

CiteScore

5.90

自引率

2.30%

发文量

176

审稿时长

4.5 months

期刊介绍： Human Cell is the official English-language journal of the Japan Human Cell Society. The journal serves as a forum for international research on all aspects of the human cell, encompassing not only cell biology but also pathology, cytology, and oncology, including clinical oncology. Embryonic stem cells derived from animals, regenerative medicine using animal cells, and experimental animal models with implications for human diseases are covered as well. Submissions in any of the following categories will be considered: Research Articles, Cell Lines, Rapid Communications, Reviews, and Letters to the Editor. A brief clinical case report focusing on cellular responses to pathological insults in human studies may also be submitted as a Letter to the Editor in a concise and short format. Not only basic scientists but also gynecologists, oncologists, and other clinical scientists are welcome to submit work expressing new ideas or research using human cells.