The profile of gene expression and role of nuclear factor kappa B on glomerular injury in rats with Thy-1 nephritis.
Mesangioproliferative glomerulonephritis (MsPGN) is a disease of high incidence in humans. Rats with Thy-1 nephritis (Thy-1 N) are used as an animal model for studying MsPGN. Although several studies have demonstrated that many pathological factors could cause the injury of glomerular mesangial cells (GMCs) in Thy-1 N, changes of profile and the molecular mechanism of the disease (i.e. the role of transcription factors) at intervals remain unclear. The purpose of this study was to identify the changes in gene expression profile and to observe the role of nuclear factor kappa B (NF-kappaB) on the pathological change of renal tissue in Thy-1 N rats. Our results showed that the pathological changes of GMCs in Thy-1 N included three phases: apoptosis (40 min), necrosis (24 h) and proliferation (7 days). Concomitantly, at 40 min and on day 7, the up-regulation of 341 genes and 250 genes were observed, while 392 genes and 119 genes were down-regulated in Thy-1 N. Expression of interleukin (IL)-1beta, IL-6, proliferating cell nuclear antigen, alpha-smooth muscle actin, collagen type IV and excretion of urinary protein was increased in rats with Thy-1 N and decreased in pyrrolidine dithiocarbamate-treated rats with Thy-1 N. These data indicated that the significant changes in the gene profile were coupled with the pathological changes of Thy-1 N, and activation of NF-kappaB may contribute to the pathogenesis of GMCs apoptosis, proliferation, extracelluar matrix accumulation and proteinuria in Thy-1 N.
Wang
H
H
Department of Microbiology and Immunology, Nanjing Medical University, Nanjing, Jiangsu, China.
Jiang
X M
XM
Xu
J H
JH
Xu
J
J
Tong
J X
JX
Wang
Y W
YW
D000199:Actins / Q000378:metabolism; D000818:Animals; D024141:Collagen Type IV / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D020869:Gene Expression Profiling / Q000379:methods; D005786:Gene Expression Regulation; D015432:Glomerulonephritis, Membranoproliferative / Q000188:drug therapy / Q000276:immunology / Q000378:metabolism*; D053583:Interleukin-1beta / Q000096:biosynthesis; D015850:Interleukin-6 / Q000096:biosynthesis; D007518:Isoantibodies / Q000276:immunology; D007678:Kidney Glomerulus / Q000276:immunology; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism; D011507:Proteinuria / Q000517:prevention & control; D011759:Pyrrolidines / Q000627:therapeutic use; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D013859:Thiocarbamates / Q000627:therapeutic use; D018800:Thy-1 Antigens / Q000276:immunology
D000199:Actins; D024141:Collagen Type IV; D053583:Interleukin-1beta; D015850:Interleukin-6; D007518:Isoantibodies; D016328:NF-kappa B; D018809:Proliferating Cell Nuclear Antigen; D011759:Pyrrolidines; D012333:RNA, Messenger; D013859:Thiocarbamates; D018800:Thy-1 Antigens; C035678:anti-Thy antibody; C498862:Acta2 protein, rat; C020972:pyrrolidine dithiocarbamic acid