Bone marrow mesenchymal stem cells repress renal transplant immune rejection by facilitating the APRIL phosphorylation to induce regulation B cell production.

Bone marrow mesenchymal stem cells (BMSCs) exert pivotal roles in suppressing immune rejection in organ transplantation. However, the function of BMSCs on immune rejection in renal transplantation remains unclear. This study aimed to evaluate the effect and underlying mechanism of BMSCs on immune rejection in renal transplantation. Following the establishment of the renal allograft mouse model, the isolated primary BMSCs were injected intravenously into the recipient mice. Enzyme-linked immunosorbent assay, flow cytometry, hematoxylin-eosin staining, and Western blot assays were conducted to investigate BMSCs' function in vivo and in vitro. Mechanistically, the underlying mechanism of BMSCs on immune rejection in renal transplantation was investigated in in vivo and in vitro models. Functionally, BMSCs alleviated the immune rejection in renal transplantation mice and facilitated B cell activation and the production of IL-10+ regulatory B cells (Bregs). Furthermore, the results of mechanism studies revealed that BMSCs induced the production of IL-10+ Bregs by facilitating a proliferation-inducing ligand (APRIL) phosphorylation to enhance immunosuppression and repressed renal transplant rejection by promoting APRIL phosphorylation to induce IL-10+ Bregs. BMSCs prevent renal transplant rejection by facilitating APRIL phosphorylation to induce IL-10+ Bregs.

Over-expressed microRNA-181a reduces glomerular sclerosis and renal tubular epithelial injury in rats with chronic kidney disease via down-regulation of the TLR/NF-κB pathway by binding to CRY1.

BACKGROUND: MicroRNAs (miRNAs) contribute to the progression of chronic kidney disease (CKD) by regulating renal homeostasis. This study explored the effects of miR-181a on CKD through the Toll-like receptor (TLR)/nuclear factor-kappa B (NF-κB) pathway by binding to CRY1. METHODS: Seventy male rats were selected and assigned into specific groups: miR-181a mimic, miR-181a inhibitor, and siRNA against CRY1, with each group undergoing different treatments to investigate many different outcomes. First, 24-h urinary protein was measured. ELISA was used to determine the serum levels of SOD, ROS, MDA, IL-1ß, IL-6, and TNF-α. Biochemical tests for renal function were performed to measure albumin, uric acid, and urea in urine and urea nitrogen and creatinine in serum. The glomerulosclerosis index (GSI) and renal tubular epithelial (RTE) cell apoptosis were detected using PASM staining and TUNEL staining, respectively. Finally, RT-qPCR and western blot were done to determine miR-181a, CRY1, TLR2, TLR4, and NF-κB expression. RESULTS: CRY1 is the target gene of miR-181a, according to a target prediction program and luciferase assay. Rats diagnosed with CKD presented increases in 24-h urinary protein; GSI; RTE cell apoptosis rate; serum ROS, MDA, IL-1ß, IL-6, and TNF-α; and CRY1, TLR2, TLR4, and NF-κB expression, as well as decreases in SOD level and miR-181a expression. Following transfection with either the miR-181a mimic or si-CRY1, 24-h urinary protein, renal damage, GSI, and cell apoptosis rate were all decreased. In addition, the overexpression of miR-181a or inhibition of CRY1 alleviated the degree of kidney injury through suppression of the TLR/NF-κB pathway. CONCLUSION: miR-181a alleviates both GS and RTE injury in CKD via the down-regulation of the CRY1 gene and the TLR/NF-κB pathway.