Gene expression profile and overexpression of apoptosis-related genes (NGFI-B and Gadd 45 gamma) in early phase of Thy-1 nephritis model.
Mesangioproliferative glomerulonephritis (MPGN) is a disease of high incidence in humans. Rat Thy-1 nephritis (Thy-1 N), namely, anti-thymocyte serum (ATS)-induced nephritis, is considered to be an animal model for studying MPGN. Although previous studies have demonstrated that glomerular mesangial cell (GMCs) injury might be a feature of Thy-1 N, the mechanism of the disease (i.e., GMC apoptosis) remains unclear. We have examined the pathologic changes of GMCs and the gene expression profile of renal tissues in Thy-1 N. The pathologic changes of Thy-1 N include three phages: GMC apoptosis (40 min), necrosis (2 h), and proliferation (5 days). Many TUNEL-positive cells are found 40 min after administration of ATS. Concomitantly, 341 genes are up-regulated, whereas 392 genes are down-regulated, as shown by microarrays analysis. The mRNA and protein of two of the up-regulated genes (nerve growth factor induced protein I-B, NGFI-B; growth arrest- and DNA-damage-inducible protein 45 gamma, Gadd 45 gamma) in the GMC apoptotic phase of Thy-1 N are markedly elevated, as observed by real-time polymerase chain reaction and immunohistochemistry. Our data indicate that pathologic changes of Thy-1 N are involved in the abnormal gene profile. The overexpression of the NGFI-B and Gadd 45 gamma genes may be associated with GMC apoptosis of Thy-1 N.
Xu
Jing-hua
JH
Department of Immunology, Nanjing Medical University, Nanjing Hanzhong Road 140, Jiangsu Province, 210029, People's Republic of China.
Qiu
Wen
W
Wang
Ying-wei
YW
Xu
Juan
J
Tong
Jian-xia
JX
Gao
Ling-juan
LJ
Xu
Wen-huang
WH
Wu
Yi-qin
YQ
D000818:Animals; D000961:Antilymphocyte Serum / Q000008:administration & dosage / Q000633:toxicity*; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics; D004268:DNA-Binding Proteins / Q000096:biosynthesis* / Q000235:genetics; D020869:Gene Expression Profiling / Q000379:methods; D005786:Gene Expression Regulation / Q000187:drug effects / Q000235:genetics; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D050527:Mesangial Cells / Q000378:metabolism / Q000473:pathology; D009393:Nephritis / Q000139:chemically induced / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D057105:Nuclear Receptor Subfamily 4, Group A, Member 1; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods; D011817:Rabbits; D051381:Rats; D018160:Receptors, Cytoplasmic and Nuclear / Q000096:biosynthesis* / Q000235:genetics; D011987:Receptors, Steroid / Q000096:biosynthesis* / Q000235:genetics; D014157:Transcription Factors / Q000096:biosynthesis* / Q000235:genetics; D000097642:GADD45 Proteins
D000961:Antilymphocyte Serum; D004268:DNA-Binding Proteins; D047908:Intracellular Signaling Peptides and Proteins; D057105:Nuclear Receptor Subfamily 4, Group A, Member 1; D018160:Receptors, Cytoplasmic and Nuclear; D011987:Receptors, Steroid; D014157:Transcription Factors; D000097642:GADD45 Proteins; C539821:NR4A1 protein, human; C539820:Nr4a1 protein, rat