Impact of high salt diets on CHOP-mediated apoptosis and renal fibrosis in a rat model.

Autor: Khadive T; Biochemistry Department, School of Medicine, Zanjan University of Medical Sciences, Mahdavi Street, Zanjan, Iran., Ghadimi D; Biochemistry Department, School of Medicine, Zanjan University of Medical Sciences, Mahdavi Street, Zanjan, Iran. d.ghadimi@zums.ac.ir., Hemmati M; Biochemistry Department, School of Medicine, Zanjan University of Medical Sciences, Mahdavi Street, Zanjan, Iran., Golshahi H; Tissue Engineering Department, Nanobiotechnology Research Center, Avicenna Research Institute, Tehran, Iran.
Jazyk: angličtina
Zdroj: Molecular biology reports [Mol Biol Rep] 2021 Sep; Vol. 48 (9), pp. 6423-6433. Date of Electronic Publication: 2021 Aug 26.
DOI: 10.1007/s11033-021-06644-y
Abstrakt: Background: Prolonged and excessive salt intake accelerates oxidative stress in kidney tissues, which brings about ER stress. The PERK/ATF4/CHOP/BCL-2 signaling pathway has an essential role in ER stress-induced apoptosis. The present study aimed to investigate the effect of high salt diets on the development of renal fibrosis through CHOP-mediated apoptosis.
Methods and Results: Twenty-five male Wistar rats were randomly divided into five groups (n = 5 each). Groups 1-5 were treated with 0%, 0.5%, 1%, 1.2%, 1.5% of NaCl dissolved in distilled water, respectively, for 8 weeks. To detect the degree of renal tubular damage, urinary KIM-1 was measured. The slides of renal tissues were stained via Masson's Trichrome staining methods for fibrosis detection. The relative gene expression of ATF4, CHOP, and BCl-2 in renal tissues were analyzed using the qRT-PCR method. The results revealed no significant difference between the urea, creatinine, and urine flow rate of the rats receiving different concentrations of NaCl (groups 2-5) and those of the control group (group 1). The rats treated with 1.5% NaCl (group 5) showed significant elevations in urinary KIM-1 and the mRNA level of CHOP compared to the control group. Mild renal fibrosis was also observed in group 5.
Conclusions: Excessive salt intake leads to fibrosis as it induces the PERK/ATF4/CHOP/BCL-2 signaling pathway in renal tissues. KIM-1 is detectable in urine before the impairment of renal function which can be used as a diagnostic marker to prevent the development of progressive renal failure.
(© 2021. The Author(s), under exclusive licence to Springer Nature B.V.)
Databáze: MEDLINE
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