Apoptosis of tubulointerstitial chronic inflammatory cells in progressive renal fibrosis after cancer therapies
Author(s)
Yang, Tao
A. Vesey, David
W. Johnson, Davin
Q. Wei, Ming
C. Gobe, Glenda
Griffith University Author(s)
Year published
2007
Metadata
Show full item recordAbstract
Progressive renal fibrosis is an unwanted and limiting side effect of cancer treatments, whether they are systemic (for example, chemotherapy), local (for example, radiotherapy), or total body irradiation for allogenic bone marrow transplants. The relative roles of macrophages, myofibroblasts, and lymphocytes and the apoptotic deletion of renal functional or inflammatory cell populations in the pathogenesis of renal fibrosis are yet unclear. In this study, rat models of 2 renal cancer treatments: cis-platinum-(II)-diammine dichloride (cisplatin, 6-mg/kg body weight) and radiation (single dose of 20Gy) were used. Kidneys were ...
View more >Progressive renal fibrosis is an unwanted and limiting side effect of cancer treatments, whether they are systemic (for example, chemotherapy), local (for example, radiotherapy), or total body irradiation for allogenic bone marrow transplants. The relative roles of macrophages, myofibroblasts, and lymphocytes and the apoptotic deletion of renal functional or inflammatory cell populations in the pathogenesis of renal fibrosis are yet unclear. In this study, rat models of 2 renal cancer treatments: cis-platinum-(II)-diammine dichloride (cisplatin, 6-mg/kg body weight) and radiation (single dose of 20Gy) were used. Kidneys were analyzed 4 days to 3 months after treatment. The extent of renal fibrosis was compared with number and localization of chronic inflammatory cell populations, cell death (apoptosis and necrosis), and expression and localization of profibrotic growth factors transforming growth factor-߱ (TGF-߱) and tumor necrosis factor-alpha (TNF-a). The models provided contrasting rates of fibrogenesis: After cisplatin, development of fibrosis was rapid and extensive (up to 50% fibrosis at 3 months); in comparison, radiation-induced fibrosis was slowly progressive (approximately 10% fibrosis at 3 months). The extent of fibrosis was associated spatially and temporally with increasing numbers of myofibroblasts with TGF-߱ or macrophages with TNF-a. Tubular epithelial apoptosis was highest with high TNF-a (P < 0.05). A significant inverse correlation existed between extent of tubulointerstitial fibrosis and interstitial cell apoptosis for cisplatin and a similar nonsignificant result for radiation (r2 = 0.8671 for cisplatin, P < 0.05; r2 = 0.2935 for radiation, NS). The latter result suggests a role for inflammatory cell apoptosis in minimizing development of renal fibrosis.
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View more >Progressive renal fibrosis is an unwanted and limiting side effect of cancer treatments, whether they are systemic (for example, chemotherapy), local (for example, radiotherapy), or total body irradiation for allogenic bone marrow transplants. The relative roles of macrophages, myofibroblasts, and lymphocytes and the apoptotic deletion of renal functional or inflammatory cell populations in the pathogenesis of renal fibrosis are yet unclear. In this study, rat models of 2 renal cancer treatments: cis-platinum-(II)-diammine dichloride (cisplatin, 6-mg/kg body weight) and radiation (single dose of 20Gy) were used. Kidneys were analyzed 4 days to 3 months after treatment. The extent of renal fibrosis was compared with number and localization of chronic inflammatory cell populations, cell death (apoptosis and necrosis), and expression and localization of profibrotic growth factors transforming growth factor-߱ (TGF-߱) and tumor necrosis factor-alpha (TNF-a). The models provided contrasting rates of fibrogenesis: After cisplatin, development of fibrosis was rapid and extensive (up to 50% fibrosis at 3 months); in comparison, radiation-induced fibrosis was slowly progressive (approximately 10% fibrosis at 3 months). The extent of fibrosis was associated spatially and temporally with increasing numbers of myofibroblasts with TGF-߱ or macrophages with TNF-a. Tubular epithelial apoptosis was highest with high TNF-a (P < 0.05). A significant inverse correlation existed between extent of tubulointerstitial fibrosis and interstitial cell apoptosis for cisplatin and a similar nonsignificant result for radiation (r2 = 0.8671 for cisplatin, P < 0.05; r2 = 0.2935 for radiation, NS). The latter result suggests a role for inflammatory cell apoptosis in minimizing development of renal fibrosis.
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Journal Title
Translational Research
Volume
150
Issue
1
Subject
Clinical Sciences not elsewhere classified
Clinical Sciences