Microarray analysis of a reversible model and an irreversible model of anti-Thy-1 nephritis.
A single intravenous injection of anti-Thy-1 monoclonal antibody (mAb) 1-22-3 is known to cause reversible mesangial proliferative glomerulonephritis. However, mAb 1-22-3 injection followed by unilateral nephrectomy leads to progressive glomerulosclerosis and tubulointerstitial change with an irreversible course. To identify genes that play an important role in the irreversible progression of renal injury, we used microarray technology to identify differences in gene expression between these models. Rats were intravenously injected with mAb 1-22-3 1 week after unilateral nephrectomy (irreversible model) or a sham operation (reversible model), and rats were killed on days 4, 7, 14, 42, and 56 after the injection. complementary DNA probes prepared from kidney messenger RNAs were hybridized with oligonucleotide microarrays containing 4854 rat genes. The microarray identified 189 differentially expressed genes, having at least a two-fold difference in expression level between the two models, and they were classified into five clusters. One of the clusters consisted of genes whose expression was markedly upregulated in the irreversible model. This cluster included the genes encoding osteopontin, kidney injury molecule-1, and thymosin beta10. Increased expression of thymosin beta10 was localized mainly in macrophages in the fibrotic interstitium, and upregulation of thymosin beta10 expression was also observed in a unilateral ureteral obstruction model. The microarray analysis yielded information on the molecular mechanisms responsible for the difference in disease progression between the reversible and irreversible model of anti-Thy-1 nephritis. Thymosin beta10 may play an important role in the progression of kidney disease.
Tsuji
M
M
Department of Internal Medicine, Keio University School of Medicine, Tokyo, Japan.
Monkawa
T
T
Yoshino
J
J
Asai
M
M
Fukuda
S
S
Kawachi
H
H
Shimizu
F
F
Hayashi
M
M
Saruta
T
T
D000818:Animals; D015815:Cell Adhesion Molecules / Q000032:analysis / Q000235:genetics; D004195:Disease Models, Animal; D018450:Disease Progression; D005260:Female; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D007150:Immunohistochemistry; D007518:Isoantibodies; D007668:Kidney / Q000737:chemistry; D008264:Macrophages / Q000737:chemistry; D008565:Membrane Proteins / Q000032:analysis / Q000235:genetics; D005810:Multigene Family / Q000235:genetics*; D009393:Nephritis / Q000139:chemically induced / Q000235:genetics* / Q000276:immunology*; D020411:Oligonucleotide Array Sequence Analysis; D053495:Osteopontin; D012333:RNA, Messenger / Q000032:analysis / Q000235:genetics; D051381:Rats; D017208:Rats, Wistar; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012795:Sialoglycoproteins / Q000032:analysis / Q000235:genetics; D013947:Thymosin / Q000032:analysis / Q000235:genetics / Q000502:physiology
D015815:Cell Adhesion Molecules; D007518:Isoantibodies; D008565:Membrane Proteins; D053495:Osteopontin; D012333:RNA, Messenger; D012795:Sialoglycoproteins; D013947:Thymosin; C110936:Havcr1 protein, rat; C506897:Spp1 protein, rat; C035678:anti-Thy antibody; C039302:thymosin beta(10)