Neutrul Calponin (Calponin H2) Suppresses Active Interstitial Inflammation In The Kidney From Early Phase Of Experimental Diabetes Mellitus

Objiective:To study the role of neutral calponin(Calponin-h2,CN2) in the course of diabetic interstitial injury.Method:Diabetes was induced by streptozocin on both CN2-Tg C57BL/6J mice and wild type ones(WT).Body weight,blood pressure,blood glucose,24 hour urinary 8-hydroxy-2'deoxyguanosine(8-OHdG),creatinine(Cr),albumin and nephrectomy were done on 8 and 30 days after disease induction as well as on day 0.Immunohistochemical stain for proliferating cells(ki-67), macrophages(F4/80) and phenotypic change of interstitial cells(α-smooth muscle actin,α-SMA) for evaluation of interstitial inflammation on all mice and all data were evaluated by computer-analysis system.Results:CN2-Tg diabetic mice showed significantly lower excretion of 24 hour urinary 8-OHdG/Cr(ng/mg) than WT diabetic mice at day 8((1.025±0.068 in CN2-Tg vs.1.557±0.150 in WT,p＜0.05).The interstitial cell proliferation(ki-67~+ cells/high power field,hpf) was significantly suppressed in CN2-Tg at day 8(3.745±0.510 vs.5.700±0.418,p＜0.05), but not at day 30(1.142±0.442 vs.1.233±0.240,p＞0.05).Reduction of macrophages recruitment in the interstitium(F4/80~+ cells/hpf) was induced in CN2-Tg at day 8(3.697±0.143 vs.6.867±1.333,p＜0.02),and day 30 (2.193±0.702 vs.5.365±0.478,p＜0.01).There were no significant differences in bothα-SMA expression and blood pressure(both systolic and diastolic) between two groups.Conclusion:CN2 overexpression suppressed both of interstitial cell proliferation and macrophages infiltration from early phase in diabetes mellitus. Precedent anti-inflammatory property of CN2 may be critical for subsequent development of interstitial renal injuriy in diabetes mellitus and a novel target in treatment of diabetes nephropathy(DN).CN2 gene also may use in DN therapy.