Proteomic patterns and prediction of glomerulosclerosis and its mechanisms

被引:84
作者
Xu, BJ
Shyr, Y
Liang, XB
Ma, LJ
Donnert, EM
Roberts, JD
Zhang, XQ
Kon, V
Brown, NJ
Caprioli, RM
Fogo, AB
机构
[1] Vanderbilt Univ, Med Ctr, Dept Pathol, Nashville, TN 37232 USA
[2] Vanderbilt Univ, Med Ctr, Dept Canc Biol, Nashville, TN 37232 USA
[3] Vanderbilt Univ, Med Ctr, Dept Biostat, Nashville, TN 37232 USA
[4] Vanderbilt Univ, Med Ctr, Dept Pediat, Nashville, TN 37232 USA
[5] Vanderbilt Univ, Med Ctr, Dept Med, Nashville, TN 37232 USA
[6] Vanderbilt Univ, Med Ctr, Dept Biochem, Nashville, TN 37232 USA
来源
JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY | 2005年 / 16卷 / 10期
关键词
D O I
10.1681/ASN.2005030262
中图分类号
R5 [内科学]; R69 [泌尿科学(泌尿生殖系疾病)];
学科分类号
1002 ; 100201 ;
摘要
Protein expression profiles linked to sclerosis in the 5/6 nephrectomy (Nx) rat model of focal segmental glomerulosclerosis were investigated. Sections of control glomeruli from normal baseline Nx tissue and nonsclerotic and sclerotic glomeruli from 12 wk after 5/6 Nx were isolated by laser capture microdissection. Protein profiles were acquired directly by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. Classification accuracy was 99.2% for distinguishing normal versus sclerotic glomeruli and 96.7 and 97.8% for nonsclerotic versus normal and sclerotic glomeruli, respectively. The proteomic pattern of the nonsclerotic glomeruli was more similar to sclerotic than normal glomeruli (P < 0.0001). Thymosin beta 4, a protein with relevant interactions with plasminogen activator inhibitor-1, angiogenesis, and wound healing, was identified as a key differentially expressed protein. Thymosin beta 4 immunostaining was increased in sclerotic glomeruli, predominantly in endothelial cells. Downregulation of thymosin beta 4 by RNAi in cultured glomerular endothelial cells decreased angiotensin II-induced plasminogen activator inhibitor-1 expression. In conclusion, proteomic patterns can accurately distinguish normal versus nonsclerotic versus sclerotic glomeruli. The closely related proteomic patterns of nonsclerotic and sclerotic glomeruli suggest early activation of prosclerotic mechanisms even in seemingly intact glomeruli. Thymosin beta 4 is a marker of such early events and may even contribute to sclerosis.
引用
收藏
页码:2967 / 2975
页数:9
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