Podocytes are specialized cells within the glomerular filtration barrier, which are crucial for maintaining glomerular structural integrity and convective ultrafiltration. Podocytes exhibit a unique arborized morphology with foot processes interfacing by slit diaphragms, ladder-like, multimolecular sieves, which provide size and charge selectivity for ultrafiltration and transmembrane signaling. Podocyte dysfunction, resulting from oxidative stress, dysregulated prosurvival signaling, or structural damage, can drive the development of proteinuria and glomerulosclerosis in hypertensive nephropathy. Functionally, podocyte injury leads to actin cytoskeleton rearrangement, foot process effacement, dysregulated slit diaphragm protein expression, and impaired ultrafiltration. Notably, the renin-angiotensin system plays a pivotal role in podocyte function, with beneficial AT2R (angiotensin receptor 2)-mediated nitric oxide (NO) signaling to counteract AT1R (angiotensin receptor 1)-driven calcium (Ca2+) influx and oxidative stress. Disruption of this balance contributes significantly to podocyte dysfunction and drives albuminuria, a marker of kidney damage and overall disease progression. Oxidative stress can also lead to sustained ion channel-mediated Ca2+ influx and precipitate cytoskeletal disorganization. The complex interplay between GPCR signaling, ion channel activation, and redox injury pathways underscores the need for additional research aimed at identifying targeted therapies to protect podocytes and preserve glomerular function. Earlier detection of albuminuria and podocyte injury through routine noninvasive diagnostics will also be critical in populations at the highest risk for the development of hypertensive kidney disease. In this review, we highlight the established mechanisms of oxidative stress-mediated podocyte damage in proteinuric kidney diseases, with an emphasis on a hypertensive renal injury. We will also consider emerging therapies that have the potential to selectively protect podocytes from redox-related injury.

中文翻译：

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高血压中足细胞氧化还原损伤的机制见解。


足细胞是肾小球滤过屏障内的特化细胞，对于维持肾小球结构完整性和对流超滤至关重要。足细胞表现出独特的树状形态，足突与狭缝隔膜、梯状多分子筛相连接，为超滤和跨膜信号传导提供尺寸和电荷选择性。由氧化应激、促存活信号失调或结构损伤引起的足细胞功能障碍可驱动高血压肾病中蛋白尿和肾小球硬化的发展。在功能上，足细胞损伤导致肌动蛋白细胞骨架重排、足突消失、裂隙隔膜蛋白表达失调和超滤受损。值得注意的是，肾素-血管紧张素系统在足细胞功能中起着关键作用，有益的 AT2R（血管紧张素受体 2）介导的一氧化氮 （NO） 信号传导可抵消 AT1R（血管紧张素受体 1）驱动的钙 （Ca2+） 内流和氧化应激。这种平衡的破坏显着导致足细胞功能障碍并导致白蛋白尿，白蛋白尿是肾脏损伤和整体疾病进展的标志。氧化应激还可导致持续的离子通道介导的 Ca2+ 内流，并促进细胞骨架组织解体。GPCR 信号传导、离子通道激活和氧化还原损伤通路之间的复杂相互作用强调了需要进行更多研究，以确定靶向疗法以保护足细胞和保持肾小球功能。通过常规无创诊断及早发现白蛋白尿和足细胞损伤对于高血压肾病发展风险最高的人群也至关重要。 在这篇综述中，我们强调了蛋白尿性肾病中氧化应激介导的足细胞损伤的既定机制，重点是高血压肾损伤。我们还将考虑有可能选择性地保护足细胞免受氧化还原相关损伤的新兴疗法。