Rituximab regulates the expression of the Raf kinase inhibitor protein via NF-κB in renal tissue of rats with diabetic nephropathy.
This study aimed to investigate the expression levels of the Raf kinase inhibitor protein (RKIP) and NF-κB in renal tissues of diabetic nephropathy (DN) rats, and to determine the underlying molecular targets of rituximab (RTX), with the goal of developing new clinical treatment selection for DN. Sprague-Dawley rats were randomly divided into a normal group (N), a DN group (M), and an RTX treatment group (D). Blood glucose and 24-h urine protein levels of rats were determined. The expression levels of RKIP and NF-κB in glomerular tissues were determined by immunohistochemistry staining and Western blotting. Comparisons between the M and N groups revealed that the concentrations of blood glucose and 24-h urine protein were significantly increased by DN (P < 0.01), and the expression levels of RKIP and NF-κB were significantly decreased and increased (P < 0.05), respectively. In the D group, the expression levels of RKIP and NF-κB were, respectively, upregulated and downregulated by RTX, and the concentrations of 24-h urine protein were also decreased by RTX. These results suggest that expression levels of RKIP might be regulated by RTX via NF-κB. This pathway could play an important role in the development and pathogenesis of DN. Therefore, RTX could be selected for clinical treatment of DN.
Department of Nephrology, Affiliated Hospital of Guiyang Medical College, Guiyang, Guizhou Province, China.
L
L
Li
Y W
YW
Zhao
J S
JS
Zeng
F
F
Fan
X
X
Wang
Y
Y
Zhou
Z
Z
Zhu
D000818:Animals; D058846:Antibodies, Monoclonal, Murine-Derived / Q000008:administration & dosage*; D003921:Diabetes Mellitus, Experimental / Q000150:complications / Q000188:drug therapy* / Q000235:genetics; D003928:Diabetic Nephropathies / Q000150:complications / Q000188:drug therapy* / Q000235:genetics; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D008297:Male; D016328:NF-kappa B / Q000378:metabolism*; D049488:Phosphatidylethanolamine Binding Protein / Q000096:biosynthesis* / Q000235:genetics; D051381:Rats; D000069283:Rituximab; D015398:Signal Transduction
D058846:Antibodies, Monoclonal, Murine-Derived; D016328:NF-kappa B; D049488:Phosphatidylethanolamine Binding Protein; D000069283:Rituximab