The Effect of Allograft Inflammatory Factor-1 on Inflammation, Oxidative Stress, and Autophagy via miR-34a/ATG4B Pathway in Diabetic Kidney Disease.

Increasing evidence suggests that disorders of inflammation, oxidative stress, and autophagy contribute to the pathogenesis of diabetic kidney disease (DKD). This study attempted to clarify the effect of allograft inflammatory factor-1 (AIF-1), miR-34a, and ATG4B on inflammation, oxidative stress, and autophagy in DKD both in vitro and in vivo experiments. In vivo, it was found that the levels of AIF-1, miR-34a, oxidative stress, and inflammatory factors were significantly increased in blood and urine samples of DKD patients and mouse models and correlated with the level of urinary protein. In vitro, it was also found that the expressions of AIF-1, miR-34a, ROS, and inflammatory factors were increased, while ATG4B and other autophagy related proteins were decreased in human renal glomerular endothelial cells (HRGECs) cultured with high concentration glucose medium (30 mmol/L). When AIF-1 gene was overexpressed, the levels of miR-34a, ROS, and inflammatory factors were significantly upregulated, and autophagy-related proteins such as ATG4B were downregulated, while downregulation of AIF-1 gene had the opposite effect. In addition, miR-34a inhibited the expression of ATG4B and autophagy-related proteins and increased the levels of ROS and inflammation. Furthermore, the result of luciferase reporter assay suggested that ATG4B was the target gene of miR-34a. When ATG4B gene was overexpressed, the level of autophagy was upregulated, and inflammatory factors were downregulated. Conversely, when ATG4B gene was inhibited, the level of autophagy was downregulated, and inflammatory factors were upregulated. Then, autophagy inducers inhibited the levels of inflammation and ROS, whereas autophagy inhibitors had the opposite function in HRGECs induced by glucose (30 mmol/L). In conclusion, the above data suggested that AIF-1 regulated the levels of inflammation, oxidative stress, and autophagy in HRGECs via miR-34a/ATG4B pathway to contribute to the pathogenesis of diabetic kidney disease.

Fasudil hydrochloride prevents cisplatin-induced renal tubular epithelial cell apoptosis via Akt activation and PTEN inhibition / 中国病理生理杂志

AIM:To explore the protective effect of fasudil hydrochloride against cisplatin (CP)-induced renal tubular epithelial cell apoptosis via Akt activation and PTEN inhibition .METHODS:Healthy male Sprague-Dawley ( SD) rats were randomly divided into control group , CP group and CP+fasudil group .All animals were sacrificed 96 h after in-jection of 0.9%saline or CP .Blood samples and kidney tissues were collected to evaluate levels of blood urea nitrogen (BUN), serum creatinine (sCr) and morphological alteration of the kidneys , respectively.The apoptosis of renal tubular epithelium cells was detected by TUNEL.Protein levels of Rho-associated protein kinase 1 (ROCK1), PTEN and Akt were measured by Western blotting and immunohistochemistry .The protein level of p-Akt was analyzed by Western blotting . RESULTS:Compared with control group , the sCr and BUN levels , the expression of ROCK 1 and PTEN and TUNEL-posi-tive cells were increased , while the level of p-Akt was decreased in CP group and CP +fasudil group .The histological structure of the kidneys observed by PAS staining was developed marked structural damage in CP group (P<0.05).Com-pared with CP group, sCr level, the expression of ROCK1 and PTEN and TUNEL-positive cells were decreased, while the level of p-Akt was increased in CP+fasudil group (P<0.05).Very little structural damage was detected in fasudil-treated groups .CONCLUSION:Fasudil hydrochloride has a protective effect on CP-induced renal tubular epithelial cell apoptosis via Akt activation and PTEN inhibition 1.

Effect of aldosterone on rat peritoneal fibrosis induced by peritoneal dia-lysis / 中国病理生理杂志

AIM:To investigate the pathologic role of aldosterone and protective effect of aldosterone receptor antagonist on peritoneal fibrosis in peritoneal dialysis rats .METHODS:A peritoneal fibrosis rat model was established by intraperitoneal injection of lipopolysaccharide ( at 1 d, 3 d, 5 d and 7 d, 0.6 mg/kg) and dialysate ( daily intraperitoneal injection of 4.25%dialysate, 100 mL/kg).At the same time, spironolactone (an aldosterone receptor antagonist , 100 mg? kg -1? d-1 ) was given to the model rats .After 4 weeks, the expression of aldosterone synthase CYP 11B2, 11β-hydrox-ysteroid dehydrogenase type 2 (11β-HSD2), mineralocorticoid receptor (MCR), and inflammatory factors were detected by immunohistochemistry , real-time PCR and Western blotting .RESULTS:The rat model of peritoneal fibrosis was suc-cessfully established .At the same time, the injury of mesothelial cells , deposition of collagen fibers and thickness of perito-neal were increased .Moreover , the infiltration of macrophages in the peritoneum/dialysate was increased .The level of al-dosterone and the expression of MCR , 11β-HSD2 and CYP11B2 in fibrotic peritoneum were obviously up-regulated as com-pared with normal rats .The expression of NF-κB/MCP-1 was also increased .However , treatment with spironolactone alle-viated peritoneal fibrosis and reduced the expression of NF-κB/MCP-1.CONCLUSION:Local aldosterone is involved in the process of peritoneal fibrosis via NF-κB/MCP-1 pathway.Spironolactone alleviates peritoneal fibrosis of peritoneal dial-ysis.