Possible role of Ets-1 and MMP-1 in matrix remodeling in experimental cisplatin nephropathy.
Cisplatin is an effective antitumor drug, but nephrotoxicity has restricted its clinical use. Renal interstitial fibrosis is a major complication of cisplatin treatment, due to the increased accumulation of extracellular matrix (ECM) proteins. Ets-1 protein plays a role in matrix remodeling by regulating matrix-degrading enzymes. We studied the role of Ets-1, matrix metalloproteinase-1 (MMP-1), and interstitial collagen (type III) in experimental cisplatin nephropathy. Wistar rats ( n = 24) were treated with cisplatin (6 mg/kg), and killed on days 3, 7, and 14, along with control rats. By immunohistochemistry, a significant increase ( P < 0.02) in the number of Ets-1-positive cells (40.09 +/- 1.52) was detected in kidneys of cisplatin-treated rats on day 3, compared with the number in control rat kidneys (29.80 +/- 0.13). The number of Ets-1-positive cells decreased in kidneys from cisplatin-treated rats on days 7 (10.93 +/- 1.20) and 14 (12.16 +/- 0.60). The expression of MMP-1 showed a similar pattern, increasing on day 3, but decreasing on days 7 and 14. The decreased levels of Ets-1 and MMP-1 were associated with increased interstitial accumulation of collagen in kidneys of cisplatin-treated rats on day 14. Molecular interactions among Ets-1, MMP-1, and type III collagens might play a role in matrix remodeling in cisplatin nephropathy.
Nazneen
Arifa
A
Department of Pathology, Nagasaki University Graduate School of Medical Sciences, 1-12-4 Sakamoto, Nagasaki 852-8523, Japan.
Razzaque
Mohammed S
MS
Liu
Diange
D
Taguchi
Takashi
T
D032761:Animal Experimentation; D000818:Animals; D002945:Cisplatin / Q000494:pharmacology*; D003094:Collagen / Q000096:biosynthesis* / Q000378:metabolism; D005109:Extracellular Matrix / Q000378:metabolism; D005921:Glomerulonephritis / Q000235:genetics* / Q000473:pathology* / Q000503:physiopathology; D007150:Immunohistochemistry / Q000379:methods; D007668:Kidney / Q000187:drug effects* / Q000473:pathology / Q000648:ultrastructure; D020781:Matrix Metalloproteinase 1 / Q000502:physiology*; D050784:Proto-Oncogene Protein c-ets-1; D011518:Proto-Oncogene Proteins / Q000378:metabolism / Q000502:physiology*; D050783:Proto-Oncogene Proteins c-ets; D051381:Rats; D017208:Rats, Wistar; D014157:Transcription Factors / Q000378:metabolism / Q000502:physiology*
C494043:Ets1 protein, rat; D050784:Proto-Oncogene Protein c-ets-1; D011518:Proto-Oncogene Proteins; D050783:Proto-Oncogene Proteins c-ets; D014157:Transcription Factors; D003094:Collagen; D020781:Matrix Metalloproteinase 1; D002945:Cisplatin