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Nutrient sensing, signaling transduction, and autophagy in podocyte injury: implications for kidney disease

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Abstract

Podocytes are terminally differentiated epithelial cells of the renal glomerular tuft and these highly specialized cells are essential for the integrity of the slit diaphragm. The biological function of podocytes is primarily based on a complex ramified structure that requires sufficient nutrients and a large supply of energy in support of their unique structure and function in the glomeruli. Of note, the dysregulation of nutrient signaling and energy metabolic pathways in podocytes has been associated with a range of kidney diseases i.e., diabetic nephropathy. Therefore, nutrient-related and energy metabolic signaling pathways are critical to maintaining podocyte homeostasis and the pathogenesis of podocyte injury. Recently, a growing body of evidence has indicated that nutrient starvation induces autophagy, which suggests crosstalk between nutritional signaling with the modulation of autophagy for podocytes to adapt to nutrient deprivation. In this review, the current knowledge and advancement in the understanding of nutrient sensing, signaling, and autophagy in the podocyte biology, injury, and pathogenesis of kidney diseases is summarized. Based on the existing findings, the implications and perspective to target these signaling pathways and autophagy in podocytes during the development of novel preventive and therapeutic strategies in patients with podocyte injury-associated kidney diseases are discussed.

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Funding

This work was supported by the Research Fund from the Medical Sci-Tech Innovation Platform of Zhongnan Hospital, Wuhan University (no. PTXM2021035).

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  1. Division of Nephrology, Zhongnan Hospital of Wuhan University, 169 Donghu Road, Wuhan, 430070, Hubei, China

    Dongqing Zha & Xiaoyan Wu

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  1. Dongqing Zha
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  2. Xiaoyan Wu
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DZ: conceptualization, resources, writing-original draft, visualization, supervision. XW: writing-reviewing and editing, project administration. All authors read and approved the final manuscript.

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Correspondence to Xiaoyan Wu.

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Zha, D., Wu, X. Nutrient sensing, signaling transduction, and autophagy in podocyte injury: implications for kidney disease. J Nephrol 36, 17–29 (2023). https://doi.org/10.1007/s40620-022-01365-2

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