RESUMO
The aim of this study was to investigate the role of ferroptosis in diabetic nephropathy (DN) and the mechanism of its regulatory genes. HK-2 cells were cultured with high glucose and mice were intraperitoneally injected with streptozotocin to establish DN models. GSE111154 was analyzed to identify the abnormal expression of genes associated with DN. Cell injury was evaluated through CCK-8 assay and 4',6-diamidino-2-phenylindole/phenylindole double staining. The levels of iron, glutathione, malondialdehyde, urinary albumin, and urinary creatinine were determined by ELISA. Furthermore, western blot and RT-qPCR were used to detect protein and mRNA levels, respectively. Our data showed that heterochromatin protein 1 is an abnormally elevated gene related to DN and is further elevated by ferroptosis activators. Inhibition of HP1 significantly inhibited ferroptosis but promoted cell viability. In addition, nuclear factor erythroid2-related factor2 (NRF2) was decreased in DN cell model, but increased under the action of ferroptosis activators. NRF2 silencing reversed the protective effects of HP1 inhibition on HK-2 cells. Additionally, HP1 silencing also alleviated kidney damage in DN mice. Collectively, these findings suggest that inhibiting HP1 inhibits ferroptosis via NRF2 pathway, thereby protecting renal tubular epithelial cells from damage.
RESUMO
AIM: Henoch-Schoenlein nephritis (HSPN) is a severe disease in adults and may cause renal insufficiency in a large portion of patients. But its rarity has led to lack of data. There are few controlled studies on therapy with immunosuppressants in HSPN adults. This study aims to evaluate the effect of leflunomide on HSPN adults with nephrotic proteinuria. METHODS: We retrospectively studied 65 adult patients who had biopsy-proven HSPN with nephrotic proteinuria. Twenty-seven patients (Group P) only received steroids, and 38 (Group P + L) were treated with leflunomide in addition to steroids. The clinical features, laboratory data and pathological findings of both groups were analyzed. RESULTS: The two groups were well-matched at baseline. After 24 months of treatment, urinary protein excretion of both groups decreased significantly from the baseline, and the estimated glomerular filtration rate (eGFR) was higher in Group P + L. Four patients in Group P and three in Group P + L developed to end-stage renal disease at the most recent follow-up. Group P + L showed better renal outcome than Group P. The treatment group and the degree of mesangial hypercellularity were significantly related to renal prognosis. CONCLUSION: Leflunomide combined with steroids is effective for treating adult HSPN with nephrotic proteinuria.
