35 ± 22.67) and again increased Cilomilast order after relapse (80.69 ± 32.73) Fig D. The regulatory cytokines IL-10 and TGF-β concentration in 24 h PBMC culture were significantly high during remission compare to that of baseline and relapse values however effector cytokines IFN-ϒ and IL-4 were significantly less during remission compared to that of baseline values and again increased after relapse Fig. E, F, G, H. Conclusion: We conclude that the lower Treg, and their cytokines and higher

P-gp expression is associated with relapse of NS. MAESHIMA AKITO, MISHIMA KEIICHIRO, NAKASATOMI MASAO, SAKURAI NORIYUKI, IKEUCHI HIDEKAZU, SAKAIRI TORU, KANEKO YORIAKI, HIROMURA KEIJU, NOJIMA YOSHIHISA Department of Medicine and Clinical Science, Gunma University Graduate School of Medicine Introduction: Renal tubules are innervated by sympathetic nerves in which N-type Ca2+ channels

are densely distributed. It has been reported that sympathetic nerve activity was increased in patients with chronic renal diseases. We recently reported the increased expression Pexidartinib datasheet of N-type Ca2+ channel in the kidneys after unilateral ureteral obstruction (UUO) and the reduction of renal fibrosis by L/N-type Ca2+ channel blocker in rats (AJP Renal Physiol 304: F665–73, 2013). However, the role of N-type Ca2+ channel in renal fibrosis is not totally understood. Methods: To address this issue, we induced UUO in male mice lacking the a1B subunit

of N-type Ca2+ channel (Cav2.2) and wild type (WT) littermates and analyzed several renal fibrotic parameters in this study. Results: In C57BL/6N mice, the expression of Cav2.2 was absent in normal, find more contralateral, and sham-operated kidney, while Cav2.2 became detectable in the interstitium of the kidney after UUO. In UUO kidneys, Cav2.2 was expressed in the interstitial cells positive for alpha-SMA, a marker for myofibroblasts, but not in T-lymphocytes, Macrophages, and endothelial cells. At baseline as well as after UUO, there was no significant difference in mean blood pressure, heart rate, and renal function (serum creatinine and blood urea nitrogen levels) between WT mice and Cav2.2 mutant mice. The expression level of a-SMA in the UUO kidneys of Cav2.2 mutant mice was significantly decreased compared to that in WT mice. Cav2.2 deficiency reduced the production of fibronectin, but not type I or type III collagen in the kidney after UUO. Sirius red-positive area was significantly reduced in Cav2.2 mutant kidney compared to that in WT kidney after UUO (1.97% vs. 3.57%, P < 0.001). Conclusion: Our data suggest that Cav2.2 is implicated in myofibroblast activation and the production of extracellular matrix during renal fibrosis. Cav2.2 might be a novel therapeutic target for the treatment of fibrotic kidney disease.