Conclusion
The results suggest that basement membrane matrix, as compared with type I collagen or fibronectin matrix, prevents mesangial cells from undergoing apoptosis and promotes the survival of mesangial cells after serum deprivation or H2O2 treatment. This indicates that matrix composition infuences susceptibility to proapoptotic stimuli for mesangial cells, and is involved in the control of cell survival and death.
We have summarized our hypothesis in Fig. 4. Accumulation of extracellular matrix and progressive cell loss are the most prominent features of glomerulosclerosis. Extracellular matrix components are altered both quantitatively and qualitatively in the process leading to sclerosis. Altered matrix components may influence the susceptibility of mesangial cells to apoptotic stimuli, such as ROS. In such a situation, glomerular cells are easily lost by apoptosis.
The mechanism of glomerular cell apoptosis requires further study to enable researchers to gain new insights into the treatment of renal diseases and the prevention of subsequent glomerular scarring.
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References
Floege J, Johnson RJ, Gordon K, Iida H, Pritzl P Yoshimura A, Campbell C, Alpers CE, Couser WG. Increased synthesis of extracellular matrix in mesangial proliferative nephritis. Kidney Int 1991;40:477–488.
Border WA, Okuda S, Languino LR, Sporn MB, Ruoslahti E. Suppression of experimental glomerulonephritis by antiserum against transforming growth factor β1. Nature 1990;346:371–374.
Border WA, Ruoslahti E. Transforming growth factor-β in disease: the dark side of tissue repair. J Clin Invest 1992;90:1–7.
Desmouliere A, Redard M, Darby I, Gabbiani G. Apoptosis mediates the decrease in cellularity during the transition between granulation tissue and scar. Am J Pathol 1995;146:56–66.
Savill J. Apoptosis and the kidney. J Am Soc Nephrol 1994;5:12–21.
Savill J. Apoptosis in disease. Eur J Clin Invest 1994;24: 715–723.
Shimizu A, Kitamura H, Masuda Y, Ishizaki M, Sugisaki Y, Yamanaka N. Apoptosis in the repair process of experimental proliferative glomerulonephritis. Kidney Int 1995;47:114–121.
Baker A, Mooney A, Hughes J, Lombardi D, Johnson R, Savil J. Mesangial cell apoptosis: the major mechanism for resolution of glomerular hypercellularity in experimental mesangial proliferative nephritis. J Clin Invest 1994;94:2105–2116.
Sugiyama H, Kashihara N, Onbe T, Yamasaki Y, Wada J, Sekikawa T, Okamoto K, Kanao K, Maeshima Y, Makino H. Bcl-2 expression and apoptosis in nephrotoxic nephritis. Exper Nephrol 1997;5:481–489.
Sugiyama H, Kashihara N, Makino H, Yamasaki Y, Ota Z. Apotosis in glomerular sclerosis. Kidney Int. 1996;49: 103–111.
Makino H, Sugiyama H, Kashihara N, Sekikawa T, Onbe T, Nakajima T, Yamasaki Y, Ota Z. Apoptosis of tubular epithelial cells in rats with chronic renal failure. Med Electron Microsc 1995;28:210–212.
Makino H, Kashihara N, Sugiyama H Role of apoptosis in the progression of glomerulosclerosis. In: Koide H, Ichikawa I (eds) Progression of renal diseases. Basel: Karger, 1996:41–47.
Kashihara N, Watanabe Y, Makino H, Wallner EI, Kanwar YS Selective decreased de novo synthesis of glomerular proteoglycans under the influence of reactive oxygen species. Proc Natl Acad Sci USA 1992;89: 6309–6313.
Nath K, Croatt A, Hostetter T. Oxygen consumption and oxidant stress in surviving nephrons. Am J Physiol 1990;258:F1354-F1362.
Buttke TM, Sandstrom PA. Oxidative stress as a mediator of apoptosis. Immunol Today 1994;15:7–10.
Zhong LT, Sarafian T, Kane DJ. Bcl-2 inhibits death of central neural cells induced by multiple agents. Proc Natl Acad Sci USA 1993;90:4533–4537.
Larrick JW, Wright SC. Cyototoxic mechanism of tumor necrosis factor-α. FASEB J 1990;4:3215–3223.
Sugiyama H, Kashihara N, Makino H, Yamasaki Y, Ota Z. Reactive oxygen species induce, apoptosis in cultured human measangial cells. J Am Soc Nephrol 1996;7:2357–2363.
Johnson RJ, Iida H, Alpers CE, Majesky MW, Schwartz SM, Pritzl P, Gordon K, Gown AM. Expression of smooth muscle cell phenotype by rat mesangial cells in immune complex nephritis. J Clin Invest 1991;87:847–858.
Makino H, Kashihara N, Sugiyama H, Kanao K, Sekikawa T, Okamoto K, Maeshima Y, Ota Z, Nagai R. Phenotypic modulation of the mesangium reflected by contractile proteins in diabetes. Diabetes 1996;45:488–495
Ruoslahti E. Anchorage dependence, integrin, and apoptosis. Cell 1994;77:477–478.
Sugiyama H, Kashihara N, Sekikawa T, Makino H, Ota Z. Regulation of survival and death of mesangial cells by extracellular matrix. Kidney Int 1998;54 (in press).
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Kashihara, N., Sugiyama, H. & Makino, H. Apoptosis and scarring. Clin Exper Neph 2, 302–306 (1998). https://doi.org/10.1007/BF02480458
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DOI: https://doi.org/10.1007/BF02480458