| Budget Amount *help |
¥2,540,000 (Direct Cost: ¥2,300,000、Indirect Cost: ¥240,000)
Fiscal Year 2007: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2006: ¥1,500,000 (Direct Cost: ¥1,500,000)
|
|---|
| Research Abstract |
Basic calponin (calponin-h1), smooth muscle differentiation-specific gene, may improve the glomerular response to injury. To the contrary, there was no evidence about calponion-h2 isoform, on the effect of kidney disease. Neutral calponin (Calponin-h2, CN2) is a non-smooth muscle isoform, and a may play a physiological role in cytoskeletal organization. CN2 also powerfully suppresses smooth muscle cell migration. We hypothesized that CN2 is involved in the course of diabetic interstitial injury. We established CN2 transgenic (CN2-Tg) mouse with the CRE-loxP site-specific recombination system, in that CN2 expression is induced only during the treatment of cadmium sulfate (0.5mg/kg BW/day). Diabetes was induced by streptozocin (STZ, 100mg/kg BW x 2 times/3days) on both of CN2-Tg mouse and wild type ones (WT). Cadmium sulfate intraperitoneal treatment was started 5 days before the first STZ injection. Nephrectomy was done on 8 and 30 days after disease induction as well as on day 0 (n=6 i
… More
n each). Immunostaining for proliferating cells (ki-67), macrophages (F4/80) and phenotypic change of interstitial cells (a-smooth muscle actin, aSMA) for evaluation of interstitial inflammation on all mice and all data were evaluated by computer-analysis system.
The interstitial cell proliferation (ki-67^+ cells/high power field, hpf) was significantly suppressed in CN2-Tg at day 8 (3.7±0.5 (m±SE) in CN2-Tg, vs 5.7±0.4 in WT, p<0.05), but not at day 30 (1.1±0.4 vs 1.2±0.2). Reduction of macrophages recruitment in the interstitium (F4/80^+ cells/hpf) was induced in CN2-Tg at day 8 (3.7±0.1 vs 6.9±1.3, p<0.02), and day 30 (2.2±0.7 vs 5.4±0.5, p<0.01). There was no significant difference in both of aSMA expression and blood pressure (both systolic and diastolic) between two groups. Thus, CN2 overexpression suppressed both of interstitial cell proliferation and macrophages infiltration from early phase in diabetes mellitus.
In conclusion, precedent anti-inflammatory property of CN2 may be critical for subsequebt development of interstitial renal injuriy in diabetes mellitus. Less
|
