title: [Down-regulation of p38 MAPK and collagen by 1, 25-(OH)2-VD3 in rat models of diabetic nephropathy].
abstract: Objective To investigate the effect of 1, 25-(OH)2-VD3 on collagen type III (Col3), collagen type IV (Col4) and p38 mitogen-activated protein kinase (p38 MAPK) in rat models of type 2 diabetic nephropathy, and explore the relationships of p38MAPK with Col3 and Col4. Methods Rat models of type 2 diabetic nephropathy were induced by streptozocin (STZ, 30 mg/kg) combined with high-glucose-and-fat diet. Sixty rats were randomly divided into control group, model group, 1, 25-(OH)2-VD3 treatment group [given 1, 25-(OH)2-VD3 6 ng/(100 g.d) after modeling] and insulin group (given 2-3 U insulin after modeling). After 8 weeks' intervention, serum creatinine (Scr), blood urea nitrogen (BUN) and 24-hour proteinuria were detected in all groups. Periodic acid-Schiff (PAS) staining was used to observe the kidney pathological changes, and immunohistochemical staining and Western blotting were performed to determine p38 MAPK Col3 and Col4 expressions in rat renal interstitium. Spearman method was applied to the correlation analysis. Results Compared with the model group, blood glucose, Scr, BUN, 24-hour proteinuria and impaired renal interstitial area were all reduced in the 1, 25-(OH)2-VD3 treatment group and the insulin group. Compared with the control group, the expressions of Col3, Col4 and p38 MAPK were higher in the model group, and lower in the 1, 25-(OH)2-VD3 treatment group and the insulin group. Correlation analysis showed that 24-hour proteinuria was positively related with p38 MAPK, Col3, Col4 and immunohistochemical results; p38MAPK was positively correlated with Col3 and Col4 expressions. Conclusion Col3, Col4 and p38MAPK are up-regulated in rat models of type 2 diabetic nephropathy. The 1, 25-(OH)2-VD3 might attenuates the progression of renal interstitial fibrosis via down-regulating p38 MAPK, Col3 and Col4.
authors.affiliation: Department of Immunology, Guizhou Medical University, Guiyang 550004, China.
authors.forename: Xianhui
authors.initials: X
authors.lastname: Xie
authors.affiliation: Department of Nephrology, Second Affiliated Hospital, Guiyang College of Traditional Chinese Medical, Guiyang 550003, China.
authors.forename: Zhengsheng
authors.initials: Z
authors.lastname: Li
authors.affiliation: Institute of Kidney and Urology, Guizhou People's Hospital, Guiyang 550002, China.
authors.forename: Mingjing
authors.initials: M
authors.lastname: Pi
authors.affiliation: Institute of Kidney and Urology, Guizhou People's Hospital, Guiyang 550002, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Wu
authors.affiliation: Institute of Kidney and Urology, Guizhou People's Hospital, Guiyang 550002, China.
authors.forename: Wen
authors.initials: W
authors.lastname: Zeng
authors.affiliation: Department of Immunology, Guizhou Medical University, Guiyang 550004, China. *Corresponding authors, E-mail: zhayan72@126.com.
authors.forename: Li
authors.initials: L
authors.lastname: Zuo
authors.affiliation: Department of Immunology, Guizhou Medical University, Guiyang 550004; Institute of Kidney and Urology, Guizhou People's Hospital, Guiyang 550002, China. *Corresponding authors, E-mail: zuoligymc@163.com.
authors.forename: Yan
authors.initials: Y
authors.lastname: Zha
mesh_terms: D000818:Animals; D001806:Blood Urea Nitrogen; D015153:Blotting, Western; D002117:Calcitriol / Q000494:pharmacology*; D024061:Collagen Type III / Q000378:metabolism*; D024141:Collagen Type IV / Q000378:metabolism*; D003404:Creatinine / Q000097:blood; D003921:Diabetes Mellitus, Experimental / Q000139:chemically induced / Q000150:complications; D003928:Diabetic Nephropathies / Q000150:complications / Q000188:drug therapy* / Q000378:metabolism; D004195:Disease Models, Animal; D015536:Down-Regulation / Q000187:drug effects; D007004:Hypoglycemic Agents / Q000494:pharmacology; D007150:Immunohistochemistry; D007328:Insulin / Q000494:pharmacology; D007668:Kidney / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D011507:Proteinuria / Q000378:metabolism; D051381:Rats; D013311:Streptozocin; D014815:Vitamins / Q000494:pharmacology; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism*
chemical_list: D024061:Collagen Type III; D024141:Collagen Type IV; D007004:Hypoglycemic Agents; D007328:Insulin; D014815:Vitamins; D013311:Streptozocin; D003404:Creatinine; D048051:p38 Mitogen-Activated Protein Kinases; D002117:Calcitriol