Rabbit Anti-Human Collagen I (a.a. 1200-1217) Polyclonal antibody

Angiotensin II ( Ang II) is known to play a pivotal role in the development of diabetic nephropathy. However, the precise mechanism of Ang II-mediated effects on diabetic nephropathy is still unknown. We have reported that Smad1 plays a key role in diabetic mesangial matrix expansion and directly regulates the transcription of type IV collagen ( Col4) in vitro and in vivo. Here we examined the effect of Ang II on the expression of Smad1 and mesangial matrix expansion in streptozotocin ( STZ)-induced diabetic rats in vivo, using Ang II type 1 receptor blocker, olmesartan. We also examined the signaling mechanism by which Ang II induces mesangial matrix expansion in vitro. Treatment of diabetic rats with low-dose olmesartan for 20 weeks reduced albuminuria and hyperfiltration without affecting blood pressure and inhibited mesangial matrix expansive changes and the expression of Col4 and smooth muscle alpha actin compared with those in untreated rats. Immunohistochemical staining and Western blotting showed that the increased expression of Smad1, phospho-Smad1, and phospho-Src was inhibited by olmesartan. Ang II induced Col4 synthesis and increased expression of phospho-Src and phospho-Smad1 in cultured mesangial cells, which was blocked by olmesartan. PP2, a Src tyrosine kinase inhibitor, and overexpression of dominant negative Src also reduced the phosphorylation of Smad1. Moreover, addition of small-interfering RNA against Src significantly reduced the phosphorylation of Smad1 and synthesis of Col4. Taken together, these results indicate that Ang II can regulate the development of mesangial matrix expansion in the early phase of diabetic nephropathy through Src and Smad1.

Objective: Intracerebroventricular (ICV) injection of interleukin-1 (IL-1) stimulates the recruitment of leukocytes into the central nervous system at different time points in juvenile versus adult mice. Our results showed that leukocytes entered brain parenchyma at 8 and 16 h after injection in juvenile and adult mice, respectively. This study compares the differential gene expression patterns of extracellular matrix and adhesion molecules in the brain of juvenile and adult mice. Methods: We analyzed these gene expressions in mice brains by microarray and real-time PCR at 2 and 8 h after ICV IL-1. Results: After ICV IL-1, the following genes were significantly upregulated in both juvenile and adult mice: LAM beta 1- 1, MMP17, TGF beta, THBS3 and VCAM1 were upregulated at 2 h after injection; LAM beta 1-1 and TGF beta were upregulated at 8 h. Additional changes were found in adult mice only: CNTN1, ECM1, ICAM1 and LAM alpha 4 were upregulated at 2 h after injection; COL4 alpha 1, MMP3 and VCAM1 were upregulated at 8 h; TIMP4 was downregulated. Comparing juvenile and adult mice, real-time PCR analysis showed that there was more induction of TGF beta at 8 h and a stronger downregulation of TIMP4 at 2 h after injection in juvenile mice. Higher expression of MMP17 was found in juvenile mice, compared to adult mice, at both 2 and 8 h after injection. Conclusions: These data show distinct expression patterns of molecules related to the extracellular matrix and adhesion molecules in juvenile versus adult mice, and suggest that increased expression of MMP17 and TGF beta and decreased expression of TIMP4 may contribute to the accelerated recruitment of leukocytes into the central nervous system in juvenile animals. Copyright (C) 2007 S. Karger AG, Basel.