ABSTRACT
Objective · To establish the Fbxo22 knockout mouse model and study the biological function of FBXO22. Methods · The Fbxo22 knockout mice were generated by CRISPR-Cas9 technology. The number, appearance, weight of different embryos and mice were measured. Meanwhile, the food intake and survival of Fbxo22-/- mice were analyzed. Results · Although the Fbxo22-/- embryos were present at approximately Mendelian ratios on embryonic day 17.5/18.5, most of them died within 48 hours of birth. Furthermore, those surviving Fbxo22-/- mice showed reduced body size and food intake and decreased life span. Conclusion · FBXO22 is an important, albeit not essential, protein for early postnatal survival and normal development.
ABSTRACT
<p><b>OBJECTIVE</b>To analyze the correlation between the expressions of vascular endothelial growth factor (VEGF) and transient receptor potential canonical 6 (TRPC6) and their role in podocyte injury in rats with diabetic nephropathy.</p><p><b>METHODS</b>Forty SD rats with diabetic nephropathy induced by intraperitoneal injection of 65 mg/kg streptozotocin were randomized equally into 5 groups, including a diabetic nephropathy model group and 4 treatment groups, with 8 normal SD rats as the normal control group. In the 4 treatment groups, the rats received intraperitoneal injections with SU5416 at 5 mg/kg or 10 mg/kg twice a week or with LY294002 at 1 mg/kg or 2 mg/kg once daily for 8 weeks. Blood glucose, serum creatinine, blood urea nitrogen, and 24-h urinary protein levels of the rats were detected at different time points, and the pathologies in the renal tissue were observed using HE staining, PAS staining and immunohistochemistry. The expressions of VEGF, nephrin, and TRPC6 at mRNA and protein levels were detected using RT-PCR and Western blotting.</p><p><b>RESULTS</b>Compared with normal control rats, the diabetic rats showed significantly increased fasting blood glucose, serum creatinine, blood urea nitrogen and 24-h urinary protein levels with decreased expressions of nephrin mRNA and protein (P<0.05) and increased expressions of VEGF and TRPC6 (P<0.05). Compared with the untreated diabetic rats, the rats with SU5416 treatment showed increased 24-h urinary protein, urea nitrogen, and nephrin expression and decreased TRPC6 expression without significant changes in fasting blood glucose, serum creatinine, or VEGF expression. The rats treated with LY294002 showed decreased 24-h urinary protein and TRPC6 expression without significant changes in fasting blood glucose, serum creatinine, urea nitrogen, or expressions of nephrin and VEGF.</p><p><b>CONCLUSION</b>The regulatory effect of VEGF on TRPC6 can be blocked by inhibiting VEGFR-2 or blocking PI3K/Akt signaling pathway.</p>