Abstract
Taurine (TAU) is a sulfur-containing beta amino acid that is not involved in protein composition and anabolism, conditionally essential in mammals provided through diet. Growing evidence supports a protective role of TAU supply in osmoregulation, calcium flux, and reduction of inflammation and oxidant damage in renal diseases like diabetes. Endoplasmic reticulum (ER) stress, due to abnormal proteostasis, is a contributor to nephrotic syndrome and related renal damage. Here, we investigated the effect of dietary TAU (1.5% in drinking water for 15 days) in an established rat model that mimics human minimal change nephrosis, consisting of a single puromycin aminonucleoside (PAN) injection (intraperitoneally 15 mg/100 g body weight), with sacrifice after eight days. TAU limited proteinuria and podocytes foot processes effacement, and balanced slit diaphragm nephrin and glomerular claudin 1 expressions. In cortical proximal tubules, TAU improved lysosomal density, ER perimeter, restored proper ER-mitochondria tethering and mitochondrial cristae, and decreased inflammation. Remarkably, TAU downregulated glomerular ER stress markers (GRP78, GRP94), pro-apoptotic C/EBP homologous protein, activated caspase 3, tubular caspase1, and mitochondrial chaperone GRP75, but maintained anti-apoptotic HSP25. In conclusion, TAU, by targeting upstream ER stress separate from mitochondria dysfunctions at crucial renal sites, might be a promising dietary supplement in the treatment of the drug-resistant nephrotic syndrome.
Highlights
Nephrotic syndrome, which is one of the most widespread renal disorder in humans [1], includes a wide spectrum of diseases, with an idiopathic, toxic, or immunologic etiology, which is classified into four histological variants: minimal change disease (MCD), focal segmental glomerulosclerosisNutrients 2018, 10, 689; doi:10.3390/nu10060689 www.mdpi.com/journal/nutrients (FSGS), membranous nephropathy, and collapsing glomerulopathy, with different sensitivities to glucocorticoids [2]
Our results suggest that dietary TAU significantly preserves Endoplasmic reticulum (ER) and
Our results suggest that dietary TAU significantly preserves ER and mitochondria mitochondria features, promoting glomerular and tubular recovery and reducing experimental features, promoting glomerular and tubular recovery and reducing experimental puromycin-induced puromycin-induced damage in rat kidney
Summary
Nephrotic syndrome, which is one of the most widespread renal disorder in humans [1], includes a wide spectrum of diseases, with an idiopathic, toxic, or immunologic etiology, which is classified into four histological variants: minimal change disease (MCD), focal segmental glomerulosclerosisNutrients 2018, 10, 689; doi:10.3390/nu10060689 www.mdpi.com/journal/nutrients (FSGS), membranous nephropathy, and collapsing glomerulopathy, with different sensitivities to glucocorticoids [2]. Nephrotic syndrome, which is one of the most widespread renal disorder in humans [1], includes a wide spectrum of diseases, with an idiopathic, toxic, or immunologic etiology, which is classified into four histological variants: minimal change disease (MCD), focal segmental glomerulosclerosis. MCD is the major idiopathic syndrome in children below one year of age, where corticosteroids, mainly prednisolone, are the choice treatment to ensure rapid remission [3]. MCD may progress into steroid-resistant FSGS [4,5,6]. An effective treatment to stop MCD recurrence and progression to end-stage damage is still debated in the scientific community along with its pathogenesis [7]. Proteinuria is a common adverse event in primary podocytopathies due to the deranged filtration barrier that contributes to renal inefficiency [10]
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