Upregulation and function of GADD45gamma in unilateral ureteral obstruction.
We performed differential display analysis to determine transcriptional activity in the rat kidney, following unilateral ureteral obstruction and found a 12-fold increase in the expression of Growth Arrest and DNA Damage-45gamma (GADD45gamma), a stress-responsive molecule that interacts with cell-cycle proteins. GADD45gamma was strongly expressed in as little as 6 h following ureteric obstruction in the renal tubules, and was also found in kidney tissue of patients with chronic glomerulonephritis. Adenovirus-mediated expression of GADD45gamma in cultured renal tubular cells activated p38 along with a significant upregulation of C-C and C-X3-C chemokine ligands and fibrosis-related factors such as several matrix metalloproteinases, transforming growth factor-beta1, decorin, and bone morphogenetic protein 2. Silencing of GADD45gamma expression significantly blunted the upregulation of these inflammatory and fibrogenic mediators and monocyte infiltration in the ureteral obstructed rat kidney. Our study shows that GADD45gamma is quickly upregulated in the kidney with an obstructed ureter, enhancing the production of factors regulating the pathogenesis of kidney disease.
Shin
G-T
GT
Department of Nephrology, Ajou University School of Medicine, Suwon, Republic of Korea. gtshin@ajou.ac.kr
Kim
D R
DR
Lim
J-E
JE
Yim
H
H
Kim
H
H
D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D017209:Apoptosis; D049109:Cell Proliferation; D002478:Cells, Cultured; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D007674:Kidney Diseases / Q000209:etiology* / Q000235:genetics / Q000378:metabolism*; D007684:Kidney Tubules / Q000378:metabolism*; D008297:Male; D020929:Mitogen-Activated Protein Kinase Kinases / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D012333:RNA, Messenger / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics; D051381:Rats; D017208:Rats, Wistar; D014158:Transcription, Genetic; D015854:Up-Regulation; D014517:Ureteral Obstruction / Q000150:complications / Q000235:genetics / Q000378:metabolism*; D000097642:GADD45 Proteins
D047908:Intracellular Signaling Peptides and Proteins; D020929:Mitogen-Activated Protein Kinase Kinases; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D000097642:GADD45 Proteins