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- W4319915586 abstract "Sestrin2 regulates cell homeostasis and is an upstream signaling molecule for several signaling pathways. Sestrin2 leads to AMP-activated protein kinase- (AMPK-) and GTPase-activating protein activity toward Rags (GATOR) 1-mediated inhibition of mammalian target of rapamycin complex 1 (mTORC1), thereby enhancing autophagy. Sestrin2 also improves mitochondrial biogenesis via AMPK/Sirt1/peroxisome proliferator-activated receptor-gamma coactivator 1 alpha (PGC-1α) signaling pathway. Blockade of ribosomal protein synthesis and augmentation of autophagy by Sestrin2 can prevent misfolded protein accumulation and attenuate endoplasmic reticulum (ER) stress. In addition, Sestrin2 enhances P62-mediated autophagic degradation of Keap1 to release nuclear factor erythroid 2-related factor 2 (Nrf2). Nrf2 release by Sestrin2 vigorously potentiates antioxidant defense in diabetic nephropathy. Impaired autophagy and mitochondrial biogenesis, severe oxidative stress, and ER stress are all deeply involved in the development and progression of diabetic nephropathy. It has been shown that Sestrin2 expression is lower in the kidney of animals and patients with diabetic nephropathy. Sestrin2 knockdown aggravated diabetic nephropathy in animal models. In contrast, upregulation of Sestrin2 enhanced autophagy, mitophagy, and mitochondrial biogenesis and suppressed oxidative stress, ER stress, and apoptosis in diabetic nephropathy. Consistently, overexpression of Sestrin2 ameliorated podocyte injury, mesangial proliferation, proteinuria, and renal fibrosis in animal models of diabetic nephropathy. By suppressing transforming growth factor beta (TGF-β)/Smad and Yes-associated protein (YAP)/transcription enhancer factor 1 (TEF1) signaling pathways in experimental models, Sestrin2 hindered epithelial-mesenchymal transition and extracellular matrix accumulation in diabetic kidneys. Moreover, modulation of the downstream molecules of Sestrin2, for instance, augmentation of AMPK or Nrf2 signaling and inhibition of mTORC1, has been protective in diabetic nephropathy. Regarding the beneficial effects of Sestrin2 on diabetic nephropathy and its interaction with several signaling molecules, it is worth targeting Sestrin2 in diabetic nephropathy." @default.
- W4319915586 created "2023-02-11" @default.
- W4319915586 creator A5062198742 @default.
- W4319915586 date "2023-02-10" @default.
- W4319915586 modified "2023-10-18" @default.
- W4319915586 title "Sestrin2 Signaling Pathway Regulates Podocyte Biology and Protects against Diabetic Nephropathy" @default.
- W4319915586 cites W1487678213 @default.
- W4319915586 cites W1917997699 @default.
- W4319915586 cites W1976619010 @default.
- W4319915586 cites W1984621232 @default.
- W4319915586 cites W1986733210 @default.
- W4319915586 cites W1990271214 @default.
- W4319915586 cites W1991439167 @default.
- W4319915586 cites W2001568034 @default.
- W4319915586 cites W2004840945 @default.
- W4319915586 cites W2008428741 @default.
- W4319915586 cites W2022045742 @default.
- W4319915586 cites W2030120780 @default.
- W4319915586 cites W2034914597 @default.
- W4319915586 cites W2045091814 @default.
- W4319915586 cites W2046385403 @default.
- W4319915586 cites W2051719011 @default.
- W4319915586 cites W2052924362 @default.
- W4319915586 cites W2072375091 @default.
- W4319915586 cites W2079977655 @default.
- W4319915586 cites W2085933321 @default.
- W4319915586 cites W2091749551 @default.
- W4319915586 cites W2094517081 @default.
- W4319915586 cites W2095703659 @default.
- W4319915586 cites W2096250721 @default.
- W4319915586 cites W2098414680 @default.
- W4319915586 cites W2111835114 @default.
- W4319915586 cites W2121596834 @default.
- W4319915586 cites W2134272208 @default.
- W4319915586 cites W2156063260 @default.
- W4319915586 cites W2164726552 @default.
- W4319915586 cites W2171439919 @default.
- W4319915586 cites W2178894885 @default.
- W4319915586 cites W2179291431 @default.
- W4319915586 cites W2206269655 @default.
- W4319915586 cites W2231368253 @default.
- W4319915586 cites W2238778078 @default.
- W4319915586 cites W2253489394 @default.
- W4319915586 cites W2342967374 @default.
- W4319915586 cites W2462514513 @default.
- W4319915586 cites W2463961540 @default.
- W4319915586 cites W2470789902 @default.
- W4319915586 cites W2471394067 @default.
- W4319915586 cites W2479269302 @default.
- W4319915586 cites W2503152500 @default.
- W4319915586 cites W2524876219 @default.
- W4319915586 cites W2529101401 @default.
- W4319915586 cites W2531494988 @default.
- W4319915586 cites W2536321822 @default.
- W4319915586 cites W2547643921 @default.
- W4319915586 cites W2588778800 @default.
- W4319915586 cites W2596701277 @default.
- W4319915586 cites W2600348465 @default.
- W4319915586 cites W2605631009 @default.
- W4319915586 cites W2606327190 @default.
- W4319915586 cites W2608586744 @default.
- W4319915586 cites W2621022753 @default.
- W4319915586 cites W2727072968 @default.
- W4319915586 cites W2740060734 @default.
- W4319915586 cites W2765841182 @default.
- W4319915586 cites W2766100690 @default.
- W4319915586 cites W2767501672 @default.
- W4319915586 cites W2776029970 @default.
- W4319915586 cites W2777580858 @default.
- W4319915586 cites W2780475566 @default.
- W4319915586 cites W2782993961 @default.
- W4319915586 cites W2789348215 @default.
- W4319915586 cites W2790226313 @default.
- W4319915586 cites W2793922138 @default.
- W4319915586 cites W2795360915 @default.
- W4319915586 cites W2800211923 @default.
- W4319915586 cites W2802998469 @default.
- W4319915586 cites W2804400876 @default.
- W4319915586 cites W2809567029 @default.
- W4319915586 cites W2887562507 @default.
- W4319915586 cites W2889115887 @default.
- W4319915586 cites W2889179182 @default.
- W4319915586 cites W2890298129 @default.
- W4319915586 cites W2891980308 @default.
- W4319915586 cites W2892219454 @default.
- W4319915586 cites W2892332550 @default.
- W4319915586 cites W2897326053 @default.
- W4319915586 cites W2898470262 @default.
- W4319915586 cites W2898897599 @default.
- W4319915586 cites W2901759806 @default.
- W4319915586 cites W2908223750 @default.
- W4319915586 cites W2914280993 @default.
- W4319915586 cites W2914898147 @default.
- W4319915586 cites W2915007112 @default.
- W4319915586 cites W2938394881 @default.
- W4319915586 cites W2938971239 @default.
- W4319915586 cites W2945936938 @default.
- W4319915586 cites W2958396604 @default.