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.
Keywords: Angiotensin II; Autophagy; Insulin signaling; Nutritional signaling pathway; Podocyte; mTOR.
© 2022. The Author(s) under exclusive licence to Italian Society of Nephrology.