Early induction of osteoactivin expression in rat renal tubular epithelial cells after unilateral ureteral obstruction.
In this study, we examined the expression of osteoactivin in the rat kidney after unilateral ureteral obstruction. Male Wistar rats were sacrificed at 6h, and on days 1, 2, 3 and 7 after the obstruction. The renal tubular lumens gradually dilated, and marked interstitial fibrosis was confirmed histologically on day 3 after the obstruction. The expressions of osteoactivin and collagen type III were examined by quantitative real-time RT-PCR. An 8-fold increase in osteoactivin mRNA expression as compared with that in the sham-operated group was observed at 6h after the obstruction, whereas no elevation of collagen type III mRNA expression was observed at this early stage. Furthermore, semi-quantitative RT-PCR was performed to identify upregulation of expression of matrix metalloproteinase-13 mRNA relative to that in the sham-operated control, and normalized to the expression level of beta-actin. Intense osteoactivin expression localized in the dilated tubular epithelium and interstitial fibroblasts in the obstructive kidney was detected by immunohistochemistry and by in situ hybridization. These results suggested that the early-phase upregulation of osteoactivin expression in the tubular epithelium in response to renal injury might play a role in triggering renal interstitial fibrosis via activation of matrix metalloproteinase expression and collagen remodeling in rats.
Nakamura
Atsushi
A
Medicinal Research Laboratories, Taisho Pharmaceutical Co LTD, Saitama-Shi, Saitama, Japan. a.nakamura@po.rd.taisho.co.jp
Ishii
Aiko
A
Ohata
Chieri
C
Komurasaki
Toshi
T
D000199:Actins / Q000235:genetics / Q000378:metabolism; D000818:Animals; D024061:Collagen Type III / Q000235:genetics / Q000378:metabolism; D004195:Disease Models, Animal; D004847:Epithelial Cells / Q000378:metabolism* / Q000473:pathology; D005347:Fibroblasts / Q000378:metabolism / Q000473:pathology; D005355:Fibrosis / Q000378:metabolism / Q000473:pathology; D019084:Fluorescent Antibody Technique, Indirect; D015870:Gene Expression; D006801:Humans; D017403:In Situ Hybridization; D007684:Kidney Tubules / Q000378:metabolism* / Q000473:pathology; D008297:Male; D053509:Matrix Metalloproteinase 13 / Q000235:genetics / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000096:biosynthesis* / Q000235:genetics; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015854:Up-Regulation; D014517:Ureteral Obstruction / Q000378:metabolism* / Q000473:pathology
D000199:Actins; D024061:Collagen Type III; C503043:Gpnmb protein, rat; D008562:Membrane Glycoproteins; D012333:RNA, Messenger; D053509:Matrix Metalloproteinase 13