Objective To investigate the effect of vasopeptidase inhibitors (VPi) omapatrilat on renal tubulointerstitial fibrosis of 5/6 subtotal nephrectomized rats and to explore new prevention and treatment of renal lubulointerstitial fibrosis.Methods The renal subtotal ablation model was established by surgical 5/6 renal resection in male SD rats.Five animal groups included(1)STN group (subtotal nephreclomy); (2)Omap 10 mg group (10 mg?kg-1?d-1); (3)Omap 40 mg group (40 mg?kg-1?d-1) ; (4)Sham group and (5)Nornial control. Systolic arterial BP and renal function were measured periodically.Animals were sacrificed at the end of the 12th week after operation. Tubulointerstitial injury was scored semiquantitatively by morphological analysis (HE, Masson, PAS and PASM stain). Results Significant tubulointerstitial injury was noted in the STN group compared with normal group and sham group (P

Objective To investigate the mutations ACTN4 and SYNPO genes promoter in sporadic primary focal segmental glomerulosclerosis (FSGS) and to analyze the role of mutations in FSGS. Methods The study consisted of 82 Chinese primary FSGS, including 39 females and 43 males, ranged from 12 to 76 years old. Seventy volunteers were selected as healthy control group. Genomie DNA was extracted from peripheral blood cells of FSGS patients and hair of patients' parents by polymerase chain reaction (PCR) and direct sequencing to analyze ACTN4 and SYNPO gene promoter mutations. Mutations were matched with GenBank and TRANSFAC software database (www.ncbi.nlm.nih.gov; www.genometix.de; www.gene-regulation, corn). Dual luciferase assay system was used to analyze the promoter region mutations, based on PGL3-Basie vector, pRL-SV40 and PCI2 cell line. Hair DNA of novel mutation patients' parents was sequenced. Expression of alpha-actinin-4 and synaptopodin in patients' kidney tissue was examined by immunofluorescence. Results Three patients with 1-34C>T, 1-590delA and (1-1044delT)+ (I-797T >C) +(1-769A >G) heterozygous mutations were found in ACTN4 gene promoter respectively, and two patients with 1-24G>A and 1-851C>T heterozygous mutations in SYNPO gene promoter respectively. The same mutations were not found in the control group of 70 healthy people. Except one patient accepting her parents' 1-1044delT and 1-797T>C mutated chromosome respectively, no same mutations were found in patients' parents. Protein expression of alpha-actinin-4 and synaptopodin was reduced in mutated patients' kidneys. Except 1-1044delT group, luciferase activity in mutated groups decreased. (1-1044delT)+(1-797T>C)+(1-769A>G) mutation was associated with poor outcome and patient with these mutations progressed to end-stage renal failure. Conclusion Mutations of ACTN4 and SYNPO gene promoters affect gene transcription and protein translation, which may contribute to the onset of sporadic primary FSGS.