Roles of the Exogenous H2S-Mediated SR-A Signaling Pathway in Renal Ischemia/ Reperfusion Injury in Regulating Endoplasmic Reticulum Stress-Induced Autophagy in a Rat Model

Abstract

Objective: This study aims to explore the effects of the exogenous hydrogen sulfide (H₂S)-mediated scavenger receptor A (SR-A) signaling pathway on renal ischemia/reperfusion injury (IRI) by regulating endoplasmic reticulum (ER) stress-induced autophagy in rats. Methods: A total of 48 normal Sprague-Dawley (SD) rats and SR-A knockout rats were selected and divided into six groups (n = 8): wild-type (WT) + sham, WT + ischemia-reperfusion (I/R), WT + I/R + NaHS, SR-A^-/- + sham, SR-A^-/- + I/R and SR-A^-/- + I/R + NaHS. The concentrations of urinary protein, blood urea nitrogen (BUN), serum creatinine (SCR), malondialdehyde (MDA) and H₂S in renal tissue were detected. qRT-PCR and Western blotting were used to detect the mRNA and protein levels of IL-6, TGF-β, SR-A, LC3I, LC3II, P62, PERK, ATF6 and IRE1 pathway-related genes. A TUNEL assay was used to detect cell apoptosis. Electron microscopy was applied to observe the structure of renal autophagosomes. Results: Compared with the WT + sham group, in the rates of the WT + I/R group, the urine volume, urinary protein, BUN, SCR and MDA concentrations, the mRNA and protein expression of IL-6, TGF-β, LC3II/I, and ER stress pathway-related genes, the cell apoptosis index, and the number of autophagosomes were significantly increased 24 h after I/R, while P62 and SR-A protein expression and SOD and H₂S concentrations were significantly decreased (all P < 0.05). The levels of renal injury, autophagy and ER stress pathway-related genes were decreased in the WT + I/R + NaHS group but were increased in the SR-A^-/- + I/R group relative to the WT + I/R group. No significant differences were observed in the urine volume; the concentrations of urinary protein, BUN, SCR and MDA; the SOD activity; the mRNA and protein expression of IL-6, TGF-β, SR-A, GRP78, SR-A, GPR94, ATF4, IRE1, XBP1, ATF6, and eIF2α; the cell apoptosis index; or the number of autophagosomes in rats of the SR-A^-/- + I/R and SR-A^-/- + I/R + NaHS groups (all P > 0.05). Conclusion: These results demonstrate that the exogenous H₂S-mediated SR-A signaling pathway reduces renal IRI injury by up-regulating ER stress-induced autophagy in rats.

Effects of exercise and stevia on renal ischemia/reperfusion injury in rats [pdf]

“…Caspases (e.g., cysteine proteases) are the executors of apoptosis (Hussein et al, 2016;Shokeir et al, 2014). Cell damage induced by prolonged ischemia-reperfusion injury may lead to apoptosis, autophagy, necrosis, and necroptosis (Ling et al, 2017;Lopez-Neblina et al, 2005;Zhu et al, 2016). The present work demonstrates that renal I/R injury caused a marked increase in apoptotic cell death in proximal and distal tubular cells as determined by caspase 3 as a marker for apoptosis, and this result was in line with those reported by others (Hussein et al, 2016;Shokeir et al, 2014).…”

Knockdown lncRNA Neat1 regulates the activation of microglia and alleviate neuronal apoptosis through AKT/STAT3 pathway after cerebral ischemic reperfusion.

“…Ischemia-reperfusion may cause apoptosis, autophagy, necrosis and necroptosis [16][17][18]. If Ischemiareperfusion injury is severe, cell death may be induced via apoptotic or necrotic Pathways [19].…”

Delayed Ischemic Preconditioning Attenuated Renal Ischemia-Reperfusion Injury by Inhibiting Dendritic Cell Maturation

“…Plasma creatinine was measured using the improved Jaffe method (Quantichrom creatinine Assay Kit, BioAssay Systems, Hayward, CA) [20]. …”