Microarray and bioinformatic detection of novel and established genes expressed in experimental anti-Thy1 nephritis

被引:23
作者
Sadlier, DM
Ouyang, X
McMahon, B
Mu, W
Ohashi, R
Rodgers, K
Murray, D
Nakagawa, T
Godson, C
Doran, P
Brady, HR
Johnson, RJ
机构
[1] Mater Misericordiae Univ Hosp, Dept Med & Therapeut, Dublin 7, Ireland
[2] Dublin Mol Med Ctr, Dublin, Ireland
[3] Univ Coll Dublin, Dept Med & Therapeut, Conway Inst Biomol & Biomed Res, Dublin 2, Ireland
[4] Baylor Coll Med, Div Nephrol, Houston, TX 77030 USA
[5] Univ Florida, Div Nephrol Hypertens & Renal Transplantat, Gainesville, FL USA
关键词
anti-Thy1; nephritis; mesangial cell proliferation; transforming growth factor beta (TGF-beta); enigma; platelet-derived growth factor (PDGF); IgA nephropathy (IgAN);
D O I
10.1111/j.1523-1755.2005.00661.x
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
Background. Microarray technology is a powerful tool that can probe the molecular pathogenesis of renal injury. In this present study microarray analysis was used to monitor serial changes in the renal transcriptome of a rat model of mesangial proliferative glomerulonephritis. Administration of anti-Thy1 antibody results in phases of acute mesangial injury (day 2), cell proliferation (day 5), matrix expansion (days 5 and 7), and subsequent healing (day 14). Methods. Using Affymetrix (RAE230A) microarrays coupled with sequential primary biologic function-focused and secondary "baited" global cluster analysis, a cohort of established and putative novel modulators of mesangial cell turnover was identified. Results. Cluster analysis of proliferative genes identified a number of gene expression profiles. The most striking pattern was increased gene expression at day 5, a cluster that included platelet-derived growth factor (PDGF), cyclins and transforming growth factor-beta (TGF-beta). The gene expression patterns identified by primary focused cluster analysis were used as bioinformatic bait and resulted in the identification of novel families of genes such as the S100 family. The expression of established and novel genes was confirmed using reverse transcription-polymerase chain reaction (RT-PCR). Next, in vivo gene expression was compared to PDGF-stimulated mesangial cells in vitro revealing similar patterns of dysregulation. Conclusion. Transcriptomic analysis defined both known and novel molecules involved in mesangial cell proliferation in vitro and in vivo and defined a panel of molecules that are potential contributors to mesangial cell dysfunction in glomerular disease.
引用
收藏
页码:2542 / 2561
页数:20
相关论文
共 60 条
[41]   Bidirectional signaling links the Abelson kinases to the platelet-derived growth factor receptor [J].
Plattner, R ;
Koleske, AJ ;
Kazlauskas, A ;
Pendergast, AM .
MOLECULAR AND CELLULAR BIOLOGY, 2004, 24 (06) :2573-2583
[42]   Regulation of Smad signaling through a differential recruitment of coactivators and corepressors by ZEB proteins [J].
Postigo, AA ;
Depp, JL ;
Taylor, JJ ;
Kroll, KL .
EMBO JOURNAL, 2003, 22 (10) :2453-2462
[43]   Opposing functions of ZEB proteins in the regulation of the TGFβ/BMP signaling pathway [J].
Postigo, AA .
EMBO JOURNAL, 2003, 22 (10) :2443-2452
[44]   Microarray data normalization and transformation [J].
Quackenbush, J .
NATURE GENETICS, 2002, 32 (Suppl 4) :496-501
[45]  
RANKIN S, 1994, J BIOL CHEM, V269, P704
[46]   Chronic renal allograft dysfunction: The role of T cell-mediated tubular epithelial to mesenchymal cell transition [J].
Robertson, H ;
Ali, S ;
McDonnell, BJ ;
Burt, AD ;
Kirby, JA .
JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY, 2004, 15 (02) :390-397
[47]   Lipoxin A4 modifies platelet-derived growth factor-induced profibrotic gene expression in human renal mesangial cells [J].
Rodgers, K ;
McMahon, B ;
Mitchell, D ;
Sadlier, D ;
Godson, C .
AMERICAN JOURNAL OF PATHOLOGY, 2005, 167 (03) :683-694
[48]   Systematic variation in gene expression patterns in human cancer cell lines [J].
Ross, DT ;
Scherf, U ;
Eisen, MB ;
Perou, CM ;
Rees, C ;
Spellman, P ;
Iyer, V ;
Jeffrey, SS ;
Van de Rijn, M ;
Waltham, M ;
Pergamenschikov, A ;
Lee, JCE ;
Lashkari, D ;
Shalon, D ;
Myers, TG ;
Weinstein, JN ;
Botstein, D ;
Brown, PO .
NATURE GENETICS, 2000, 24 (03) :227-235
[49]  
Rozen S, 2000, Methods Mol Biol, V132, P365
[50]   Sequential extracellular matrix-focused and baited-global cluster analysis of serial transcriptomic profiles identifies candidate modulators of renal tubulointerstitial fibrosis in murine adriamycin-induced nephropathy [J].
Sadlier, DM ;
Connolly, SB ;
Kieran, NE ;
Roxburgh, S ;
Brazil, DP ;
Kairaitis, L ;
Wang, Y ;
Harris, DCH ;
Doran, P ;
Brady, HR .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2004, 279 (28) :29670-29680