Angiopoietins Modulate Endothelial Adaptation, Glomerular and Podocyte Hypertrophy after Uninephrectomy

作者：Chiang Wen Chih; Lai Chun Fu; Su Chi Ting; Peng Wei Hao; Wu Ching Fang; Chang Fan Chi; Chen Yi Ting; Lin Shuei Liong; Chen Yung Ming; Wu Kwan Dun; Lu Kuo Shyan; Tsai Tun Jun^*

来源：PLos One, 2013, 8(12): e82592.

DOI：10.1371/journal.pone.0082592

Glomerular capillary remodeling is an essential process in the development of glomerular hypertrophy. Angiopoietins, which are important regulators in angiogenesis, plays a role in the development of glomerulus during embryogenesis. Here, we evaluated the influence of angiopoietin on glomerular components and hypertrophy after uninephrectomy in adult male BALB/c mice. The actions of angiopoietin 1 or 2 were systemically antagonized by the subcutaneous administration of antagonists. We observed that the angiopoietin system was activated after uninephrectomy, and that the blockade of angiopoietin 1 or 2 decreased the activation of the angiopoietin receptor-tyrosine kinase with Ig and EGF homology domains-2-and attenuated the development of glomerular and podocyte hypertrophy. The increase in endothelial density staining (anti-CD31) following uninephrectomy was also reversed by angiopoietin 1 or 2 blockades. Glomerular basement thickness and foot process width were observed to decrease in the angiopoietin blockade groups. These changes were associated with the down regulation of the expression of genes for the glomerular matrix and basement membrane, including collagen type IV alpha 1, collagen type IV alpha 2, collagen type IV alpha 5, and laminin alpha 5. Thus, angiopoietin 1 or 2 may play an important role in the development of glomerular hypertrophy after uninephrectomy. A blockade of the angiopoietin system not only influenced the endothelium but also the podocyte, leading to diminished gene expression and morphological changes after uninephrectomy.

• 出版日期2013-12-18