Introduction. Focal segmental glomerulosclerosis (FSGS) ranks among nephrotic syndromes. Research shows that FSGS is brought about by several genes including transient receptor potential cation channel subfamily c member 6 (TRPC6). This study aimed to investigate TRPC6 gene in Iranian FSGS children. Materials and Methods. Twenty-six FSGS patients were included. They were all under 16 years old. Polymerase chain reaction amplification and sequencing were performed to examine exons 2 and 13 of TRPC6 gene. Results. Sampling was performed when the patients had a mean age of 9. 26 ± 3. 19 years. Sixteen children were boys (61. 5%); malefemale ratio was 1. 35: 1. Four patients (15. 4%) were diagnosed with TRPC6 variants. Three missense nonsynonymous mutations (C121S, D130V, and G162R) and 1 synonymous mutation (I111I) were detected. All variants were novel; in silico analysis predicted D130V and G162R as pathogenic. Patients with and without mutations were not different significantly regarding age at disease onset, sex, consanguinity, hypertension, hematuria, serum creatinine and albumin, rate of progression to kidney failure, response to steroids, and resistance to cyclosporine A and cyclophosphamide. Conclusions. This study examined exons 2 and 13 of TRPC6 gene in Iranian FSGS children. Four novel TRPC6 variants were detected; in silico analysis showed that 2 variants (D130V and G162R) could be pathogenic. It could be concluded that TRPC6 may be useful for genetic screening in Iranian FSGS children.

Objective: The purpose of this study was to investigate the effect of moderate-intensity training on the calcineurin/ nuclear factor of activated t-cells (NFAT) pathway and factors affecting it in the middle-age Wistar rats. Materials and Methods: In this experimental study, 40 young (n=10, 4-month-old) and middle-aged (n=30, 13-15 months old) Wistar rats were included in this experimental study. All young and 10 middle-aged rats did not training and served as a control comparision; while the remaining 20 middle-aged rats were trained at moderate intensity for 4-weeks (n=10) or 8-weeks (n=10) on a treadmill (speed: 16 m/minutes, slope: 0%, distance: 830 m, duration: 54 minutes). Results: Calcineurin tissue expression was increased in the middle-aged control rats compared to the young control rats (P=0. 001). Expression of sarco/endoplasmic reticulum Ca2+-ATPase (SERC2A), natriuretic peptide receptor-A (NPR-A), phospholamban (PLB), plasma membrane Ca2+ ATPase (PMCA4b), and p-AKT was significantly decreased in the heart tissue of middle-aged control compared to the young control rats (P=0. 001). Furthermore, transforming growth factor beta (TGF-β ), including transient receptor potential canonical 6 (TRPC6), were up-regulated in the heart tissue of middle-aged control compared to the young control rats (P=0. 001). However, aerobic training inhibited this pathway and reversed all changes in the trained middle-aged rats. Conclusion: Aerobic training effectively inhibited the calcineurin/NFATc pathway and modulated intracellular Ca2+ levels at least partially by restoring NPR-A, SERCA2, p-PLB, and p-AKT, and decreasing TRPC6 and TGF-β levels.

Background and Objective: Cardiac ischemia-reperfusion (IR) is one of the main causes of death in the world. Since exercise training is one of the practical ways to improve cardioprotection against these injuries, the purpose of the present study was to investigate the effect of preconditioning with a short term of high-intensity interval training on cardioprotection, left ventricular function and possible mechanisms.Materials and Methods: In this study, 48 male rats (8-10 weeks and 250-300 g) were randomly divided into 5 groups: control (C), high-intensity interval training (H), sham (Sh), control+ischemia-reperfusion (CIR) and high-intensity interval training+ischemia-reperfusion (HIR). The high-intensity interval training protocol consisted of 5 consecutive treadmill running in 6×2 min high intermittence with 85-90% vo2max and 5×2 min slow intermittence with 55-60% Vo2max. Rats in CIR and HIR groups were exposed to cardiac IR injury.Infarct size, lactate dehydrogenase, creatine kinase, Kloth, and TRPC6 expression were measured and data were analyzed by one way ANOVA and Tukey's post-hoc tests.Results: The results of this study showed a significant decrease in infarct size and enzymes of cardiac injury in the training group during IR. Also, the results demonstrated that the reduction of ventricular function in the training group (HIR) was less than CIR group. As well, the results showed the significant increase in Klotho levels after training and lower expression of TRPC6 channels during IR in training group.Conclusion: Short-term high-intensity interval training could reduce infarct size by one-third compared with the untrained group (CIR) (a decrease of 33.45%) and it could prevent noticeable reduction of cardiac function in IR injury. Based on the results, an increase in klotho following training and, consequently, lower expression of TRPC6 during IR, could be a mechanism for increasing cardioprotection and to reduce cardiac dysfunction.