nidНефрология и диализNephrology and Dialysis1680-44222618-9801Российское диализное обществоnid-1319Research ArticleОБЗОРЫ И ЛЕКЦИИREVIEWS AND LECTURESМатриксные металлопротеиназы в патогенезе острых и хронических заболеваний почек (Обзор литературы)Matrix metalloproteinases in the pathogenesis of acute and chronic kidney diseases ReviewБобковаИ. Н.BobkovaI. .noemail@neicon.ruКозловскаяЛ. В.KozlovskayaL. .noemail@neicon.ruЛиО. А.LiO. .noemail@neicon.ruМосковская Медицинская Академия им. И.М. Сеченова; г. МоскваRussian Federation200819062025102105111Copyright © Бобкова И.Н., Козловская Л.В., Ли О.А., 20252025Бобкова И.Н., Козловская Л.В., Ли О.А.Bobkova I..., Kozlovskaya L..., Li O...Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://journal.nephro.ru/jour/article/view/1319

Матриксные металлопротеиназы (ММП) (также называемые матриксинами) - семейство цинк-зависимых эндопептидаз, играющих ключевую роль в расщеплении компонентов экстрацеллюлярного матрикса (ЭЦМ), базальных мембран и ряда клеточных поверхностных белков. В физиологических условиях эти процессы необходимы для эмбрионального развития, морфогенеза, репродукции, тканевой резорбции, ангиогенеза, апоптоза и т. д. Изменение активности ММП (как увеличение, так и снижение) сопутствует многим заболеваниям человека (опухоли, фиброзирующие заболевания сердца, легких, печени и почек, артрит, язвенная болезнь желудка и т. д.). Настоящий обзор касается роли ММП в почечной патологии. Представлены последние сведения о локализации ММП и тканевых ингибиторов ММП (ТИМП) в структурах почки, анализируются нарушения в системе ММП/ТИМП при ряде острых и хронических заболеваний почек, определены возможные направления коррекции этих нарушений.

матриксные металлопротеиназытканевые ингибиторы матриксных металлопротеиназингибитор активатора плазминогена I типахронический гломерулонефритдиабетическая нефропатияострая почечная недостаточностькарцинома почкиингибиторы АПФблокаторы рецепторов ангиотензина IIReferencesAkiyama K., Shikata K., Sugimoto H. et al. Changes in serum concentrations of matrix metalloproteinases, tissue inhibitor of metalloproteinases and type IV collagen in patients various types of glomerulonephritis. Res Commun Mol Pathol Pharmacol 1997; 95: 115-128.Akiyama K., Shikata K., Sugimoto H. et al. Changes in serum concentrations of matrix metalloproteinases, tissue inhibitor of metalloproteinases and type IV collagen in patients various types of glomerulonephritis. Res Commun Mol Pathol Pharmacol 1997; 95: 115-128.Basile D.P., Fredrich K., Weihrauch H. et al. Angiostatin and matrix metalloproteinases expression following ischemic acute renal failure. Am J Physiol Renal Physiol 2004; 286: F893-F902.Basile D.P., Fredrich K., Weihrauch H. et al. Angiostatin and matrix metalloproteinases expression following ischemic acute renal failure. Am J Physiol Renal Physiol 2004; 286: F893-F902.Bauvois B., Mothu N., Nguen J. et al. Specific changes in plasma concentrations of matrix metalloproteinases-2 and 9, TIMP-1 and TGF-b1 in patients with distinct types of primary glomerulonephritis. Nephrol Dial Transplant 2007; 22: 1115-1122.Bauvois B., Mothu N., Nguen J. et al. Specific changes in plasma concentrations of matrix metalloproteinases-2 and 9, TIMP-1 and TGF-b1 in patients with distinct types of primary glomerulonephritis. Nephrol Dial Transplant 2007; 22: 1115-1122.Bhuvarahamurthy V., Kristiansen G.O., Johansen M. et al. In situ gene expression and localization of MMP1, MMP2, MMP3, MMP9 and their inhibitors TIMP1 and TIMP2 in human renal carcinoma. Oncol Rep 2006; 15:1379-1384.Bhuvarahamurthy V., Kristiansen G.O., Johansen M. et al. In situ gene expression and localization of MMP1, MMP2, MMP3, MMP9 and their inhibitors TIMP1 and TIMP2 in human renal carcinoma. Oncol Rep 2006; 15:1379-1384.Boffa J.-J., Lu J., Placier S. et al. Regression of renal vascular and glomerular fibrosis: the role of angiotensin II receptor antagonism and matrix metalloproteinases. J Am Soc Nephrol 2003; 14: 1132-1144.Boffa J.-J., Lu J., Placier S. et al. Regression of renal vascular and glomerular fibrosis: the role of angiotensin II receptor antagonism and matrix metalloproteinases. J Am Soc Nephrol 2003; 14: 1132-1144.Bolbrinker J., Markovic S., Wehland M. et al. Expression and response to angiotensin-converting enzyme inhibition of metalloproteinases 2 and 9 in renal glomerular damage in young transgenic rats with renin-dependent hypertension. (JPET) J Pharm Exp Ther 2006; 316: 8-16.Bolbrinker J., Markovic S., Wehland M. et al. Expression and response to angiotensin-converting enzyme inhibition of metalloproteinases 2 and 9 in renal glomerular damage in young transgenic rats with renin-dependent hypertension. (JPET) J Pharm Exp Ther 2006; 316: 8-16.Brown P.D., Giavazzi R. Matrix metalloproteinases inhibition: a review of anti-tumor activity. Ann Oncol 1995; 6: 967-974.Brown P.D., Giavazzi R. Matrix metalloproteinases inhibition: a review of anti-tumor activity. Ann Oncol 1995; 6: 967-974.Caron A., Desrosies R.R., Beliveau R. et al. Ischemia injury alters endothelial cell properties of kidney cortex: stimulation of MMP-9. Exp Cell Res 2005; 310: 105-116.Caron A., Desrosies R.R., Beliveau R. et al. Ischemia injury alters endothelial cell properties of kidney cortex: stimulation of MMP-9. Exp Cell Res 2005; 310: 105-116.Caron A., Desrosies R.R., Langlois S. et al. Ischemia-reperfusion injury stimulates gelatinase expression and activity in kidney glomeruli. Can J Physiol Pharmacol 2005; 83: 287-300.Caron A., Desrosies R.R., Langlois S. et al. Ischemia-reperfusion injury stimulates gelatinase expression and activity in kidney glomeruli. Can J Physiol Pharmacol 2005; 83: 287-300.Catania J.M., Chen G., Parrish A.R. Role of matrix metalloproteinases in renal pathophysiologies. Am J Physiol Renal Physiol 2007; 292: F905-F911.Catania J.M., Chen G., Parrish A.R. Role of matrix metalloproteinases in renal pathophysiologies. Am J Physiol Renal Physiol 2007; 292: F905-F911.Covington M.D., Burghardt R.C., Parrish A.R. Ischemia-induced cleavage of cagherins in NRK cells requires MT1-MMP (MMP-14). Am J Physiol Renal Physiol 2006; 290: F43-F51.Covington M.D., Burghardt R.C., Parrish A.R. Ischemia-induced cleavage of cagherins in NRK cells requires MT1-MMP (MMP-14). Am J Physiol Renal Physiol 2006; 290: F43-F51.Danielson L.A., Welford A., Harris A. Relaxin improves renal function and histology in aging Munich Wistar rats. J Am Soc Nephrol 2006; 17: 1325-1333.Danielson L.A., Welford A., Harris A. Relaxin improves renal function and histology in aging Munich Wistar rats. J Am Soc Nephrol 2006; 17: 1325-1333.Douthwaite J.A., Jonson T.S. Effects of transforming growth factor-b1 on renal extracellular matrix components and their regulating proteins. J Am Soc Nephrology 1999; 10: 2109-2119.Douthwaite J.A., Jonson T.S. Effects of transforming growth factor-b1 on renal extracellular matrix components and their regulating proteins. J Am Soc Nephrology 1999; 10: 2109-2119.Ebihara I., Nakamura T., Shimada N., Koide H. Increased plasma metalloproteinase-9 concentration precede development of microalbuminuria in non-insulin-dependent diabetes mellitus. Am J Kidney Dis 1998; 32: 544-550.Ebihara I., Nakamura T., Shimada N., Koide H. Increased plasma metalloproteinase-9 concentration precede development of microalbuminuria in non-insulin-dependent diabetes mellitus. Am J Kidney Dis 1998; 32: 544-550.Eddy A.A. Molecular insights into renal interstitial fibrosis. J Am Soc Nephrology 1996; 7: 2495-2508.Eddy A.A. Molecular insights into renal interstitial fibrosis. J Am Soc Nephrology 1996; 7: 2495-2508.Eddy A.А. Plasminogen activator inhibitor-1 and the kidney. Am J Physiol Renal Physiol 2002; 283 (2): F209-F220.Eddy A.А. Plasminogen activator inhibitor-1 and the kidney. Am J Physiol Renal Physiol 2002; 283 (2): F209-F220.Ewens K.G., George R.A., Sharma K. et al. Assessment of 115 candidate genes for diabetic nephropathy by transmission/disequilibrium test. Diabetes 2005; 54: 3305-3318.Ewens K.G., George R.A., Sharma K. et al. Assessment of 115 candidate genes for diabetic nephropathy by transmission/disequilibrium test. Diabetes 2005; 54: 3305-3318.Gomes D.E., Alonso D.F., Yoshiji H., Thorgeirsson U.P. Tissue inhibitors of metalloproteinases: structure, regulation and biological functions. Eur J Cell Biol 1997; 74 (2): 111-122.Gomes D.E., Alonso D.F., Yoshiji H., Thorgeirsson U.P. Tissue inhibitors of metalloproteinases: structure, regulation and biological functions. Eur J Cell Biol 1997; 74 (2): 111-122.Gong R., Rifair A., Tolbert E.M. et al. Hepatocyte growth factor modulates matrix metalloproteinases and plasminogen activator/plasmin proteolytic pathways in progressive renal interstitial fibrosis. J Am Soc Nephrology 2003; 14: 3047-3060.Gong R., Rifair A., Tolbert E.M. et al. Hepatocyte growth factor modulates matrix metalloproteinases and plasminogen activator/plasmin proteolytic pathways in progressive renal interstitial fibrosis. J Am Soc Nephrology 2003; 14: 3047-3060.Harendza S., Schneider A., Helmchen U. et al. Extracellular matrix deposition and cell proliferation in a model of chronic glomerulonephritis in the rat. Nephrol Dial Transplant 1999; 14: 2873-2879.Harendza S., Schneider A., Helmchen U. et al. Extracellular matrix deposition and cell proliferation in a model of chronic glomerulonephritis in the rat. Nephrol Dial Transplant 1999; 14: 2873-2879.Hirata H., Okayama N., Naito K. et al. Association of gaplotype of metalloproteinase (MMP)-1 and MMP-3 polymorphisms with renal cell carcinoma. Carcinogenesis 2004; 25: 2379-2384.Hirata H., Okayama N., Naito K. et al. Association of gaplotype of metalloproteinase (MMP)-1 and MMP-3 polymorphisms with renal cell carcinoma. Carcinogenesis 2004; 25: 2379-2384.Inada A., Nagai K., Arai H. et al. Establishment of a diabetic mouse model with progressive diabetic nephropathy. Am J Pathol 2005; 167: 327-336.Inada A., Nagai K., Arai H. et al. Establishment of a diabetic mouse model with progressive diabetic nephropathy. Am J Pathol 2005; 167: 327-336.Kanauchi M., Nishioka H., Nakashima Y. et al. Role of tissue inhibitors of metalloproteinase in diabetic nephropathy. Nippon Jinzo Gakkai Shi 1996; 38: 124-128.Kanauchi M., Nishioka H., Nakashima Y. et al. Role of tissue inhibitors of metalloproteinase in diabetic nephropathy. Nippon Jinzo Gakkai Shi 1996; 38: 124-128.Krag S., Nyengaard J.R., Wogensen L. Combined effects of moderately elevated blood glucose and locally produced TGF-b1 on glomerular morphology and renal collagen production. Nephrol Dial Transplant 2007; 22: 2485-2496.Krag S., Nyengaard J.R., Wogensen L. Combined effects of moderately elevated blood glucose and locally produced TGF-b1 on glomerular morphology and renal collagen production. Nephrol Dial Transplant 2007; 22: 2485-2496.Kugler A., Hemmerlein B., Thelen P. et al. Expression of metalloproteinase 2 and 9 and their inhibitors in renal cell carcinoma. J Urol 1998; 160: 1914-1918.Kugler A., Hemmerlein B., Thelen P. et al. Expression of metalloproteinase 2 and 9 and their inhibitors in renal cell carcinoma. J Urol 1998; 160: 1914-1918.Lelong B., Legallicierr B., Piedagnel R., Ronco P.M. Do matrix metalloproteinases MMP-2 and MMP-9 (gelatinases) play a role in renal development, physiology and glomerular diseases? Curr Opin Nephrol Hypertens 2001; 10: 7-12.Lelong B., Legallicierr B., Piedagnel R., Ronco P.M. Do matrix metalloproteinases MMP-2 and MMP-9 (gelatinases) play a role in renal development, physiology and glomerular diseases? Curr Opin Nephrol Hypertens 2001; 10: 7-12.Liu Y. Renal fibrosis: new insights into the pathogenesis and therаpeutics. Kidney International 2006: 69: 213-217.Liu Y. Renal fibrosis: new insights into the pathogenesis and therаpeutics. Kidney International 2006: 69: 213-217.Lods N., Ferrari P., Frey F.J. et al. Angiotensin-converting enzyme inhibition but not angiotensin receptor blockade regulates matrix metalloproteinases activity in patients with glomerulonephritis. J Am Soc Nephrol 2003; 14: 2861-2872.Lods N., Ferrari P., Frey F.J. et al. Angiotensin-converting enzyme inhibition but not angiotensin receptor blockade regulates matrix metalloproteinases activity in patients with glomerulonephritis. J Am Soc Nephrol 2003; 14: 2861-2872.Ma L.-J., Nakamura S., Aldigier J.C. et al. Regression of glomerulosclerosis with high-dose angiotensin inhibition is linked to decreased plasminogen activator inhibitor-1. J Am Soc Nephrol 2005; 16: 966-976.Ma L.-J., Nakamura S., Aldigier J.C. et al. Regression of glomerulosclerosis with high-dose angiotensin inhibition is linked to decreased plasminogen activator inhibitor-1. J Am Soc Nephrol 2005; 16: 966-976.Marti H.P. Role of matrix metalloproteinases in the progression of renal lesion. Press Med 2000; 29: 811-817.Marti H.P. Role of matrix metalloproteinases in the progression of renal lesion. Press Med 2000; 29: 811-817.Martin J., Eynstone L., Davies M., Steadman R. Induction of matrix metalloproteinases by glomerular mesangial cells stimulated by proteins of the extracellular matrix. J Am Soc Nephrol 2001; 12: 88-96.Martin J., Eynstone L., Davies M., Steadman R. Induction of matrix metalloproteinases by glomerular mesangial cells stimulated by proteins of the extracellular matrix. J Am Soc Nephrol 2001; 12: 88-96.Miyake H., Hara I., Gohji K. et al. Relative expression of matrix matrix metalloproteinase-2 and tissue inhibitor of metalloproteinase-2 in mouse renal cell carcinoma cells regulates their metastatic potential. Clin Cancer Res 1999; 5: 2824-2829.Miyake H., Hara I., Gohji K. et al. Relative expression of matrix matrix metalloproteinase-2 and tissue inhibitor of metalloproteinase-2 in mouse renal cell carcinoma cells regulates their metastatic potential. Clin Cancer Res 1999; 5: 2824-2829.McLennan S.V., Kelly D.J., Cox A.J. et al. Decreased matrix degradation in diabetic nephropathy: effects of ACE inhibition on the expression and activities of matrix metalloproteinases. Diabetologia 2002; 45: 268-275.McLennan S.V., Kelly D.J., Cox A.J. et al. Decreased matrix degradation in diabetic nephropathy: effects of ACE inhibition on the expression and activities of matrix metalloproteinases. Diabetologia 2002; 45: 268-275.McMillan J.I., Riordan J.W., Couser W.G. et al. Characterisation of a glomerular epithelial cell matrix metalloproteinase as matrix metalloproteinase-9 with enhanced expression in a model of membranous nephropathy. J Clin Invest 1996; 97: 1094-1101.McMillan J.I., Riordan J.W., Couser W.G. et al. Characterisation of a glomerular epithelial cell matrix metalloproteinase as matrix metalloproteinase-9 with enhanced expression in a model of membranous nephropathy. J Clin Invest 1996; 97: 1094-1101.Nagase H., Woessner J.F. Matrix metalloproteinases. J Biol Chem 1999; 274 (31): 21491-21494.Nagase H., Woessner J.F. Matrix metalloproteinases. J Biol Chem 1999; 274 (31): 21491-21494.Nakopoulou L., Lazaris A.C., Boletis J. et al. The matrix metalloproteinase-11 protein in various types of glomerulonephritis. Nephrol Dial Transplant 2007; 22: 109-117.Nakopoulou L., Lazaris A.C., Boletis J. et al. The matrix metalloproteinase-11 protein in various types of glomerulonephritis. Nephrol Dial Transplant 2007; 22: 109-117.Negri A.L. Prevention of progressive fibrosis in chronic renal diseases: antifibrotic agents. J Nephrol 2004; 17: 496-503.Negri A.L. Prevention of progressive fibrosis in chronic renal diseases: antifibrotic agents. J Nephrol 2004; 17: 496-503.Rerolle J.P., Hertig A., Nguyen G. et al. Plasminogen activator inhibitor I is a potential target in renal fibrogenesis. Kidney Int 2000; 58: 1841-1850.Rerolle J.P., Hertig A., Nguyen G. et al. Plasminogen activator inhibitor I is a potential target in renal fibrogenesis. Kidney Int 2000; 58: 1841-1850.Romanic A.M., Burns-Kurtis C.L., Ao Z. et al. Upregulated expression of human membrane type-5 matrix metalloproteinase in kidneys from diabetic patients. Am J Physiol Renal Physiol 2001; 281: F309-F317.Romanic A.M., Burns-Kurtis C.L., Ao Z. et al. Upregulated expression of human membrane type-5 matrix metalloproteinase in kidneys from diabetic patients. Am J Physiol Renal Physiol 2001; 281: F309-F317.Ruiz-Ortega M., Ruperez M., Esteban V. et al. Angiotensin II: a key factor in the inflammatory and fibrotic response in kidney diseases. Nephrol Dial Transplant 2006; 21: 12-20.Ruiz-Ortega M., Ruperez M., Esteban V. et al. Angiotensin II: a key factor in the inflammatory and fibrotic response in kidney diseases. Nephrol Dial Transplant 2006; 21: 12-20.Samuel C.S. Relaxin: antifibrotic properties and effects in models of diseases. Clin Med Research 2005; 4: 241-249.Samuel C.S. Relaxin: antifibrotic properties and effects in models of diseases. Clin Med Research 2005; 4: 241-249.Sanders J-S.F., Goor H., Hanemaaijer R. et al. Renal expression of matrix metalloproteinases in human ANCA-associated glomerulonephritis. Nephrol Dial Transplant 2004; 19: 1412-1419.Sanders J-S.F., Goor H., Hanemaaijer R. et al. Renal expression of matrix metalloproteinases in human ANCA-associated glomerulonephritis. Nephrol Dial Transplant 2004; 19: 1412-1419.Sherief M.H., Low S.H., Miura M. et al. Matrix metalloproteinase activity in urine patients with renal cell carcinoma leads to degradation of extracellular matrix proteins: possible use as screening assay. J Urol 2003; 169: 1530-1534.Sherief M.H., Low S.H., Miura M. et al. Matrix metalloproteinase activity in urine patients with renal cell carcinoma leads to degradation of extracellular matrix proteins: possible use as screening assay. J Urol 2003; 169: 1530-1534.Steinmann N.K., Ziswiller R., Kung M. et al. Inhibition of matrix metalloproteinases attenuates anti-Thy 1.1 nephritis. J Am Soc Nephrology 1998; 9: 397-407.Steinmann N.K., Ziswiller R., Kung M. et al. Inhibition of matrix metalloproteinases attenuates anti-Thy 1.1 nephritis. J Am Soc Nephrology 1998; 9: 397-407.Sutton T.A., Kelly K.J., Mang H.E. et al. Minocycline reduces renal microvascular leakage in a rat model of ischemic renal injury. Am J Physiol Renal Physiol 2005; 288: F91-F97.Sutton T.A., Kelly K.J., Mang H.E. et al. Minocycline reduces renal microvascular leakage in a rat model of ischemic renal injury. Am J Physiol Renal Physiol 2005; 288: F91-F97.Tashiro K., Koynagi I., Ohara I. et al. Levels of urinary matrix metalloproteinase-9 (MMP-9) and renal injuries in patients with type 2 diabetic nephropathy. J Clin Lab Anal 2004; 18: 206-210.Tashiro K., Koynagi I., Ohara I. et al. Levels of urinary matrix metalloproteinase-9 (MMP-9) and renal injuries in patients with type 2 diabetic nephropathy. J Clin Lab Anal 2004; 18: 206-210.Turk J., Pollock A.S., Lee L.K et al. Matrix metalloproteinase 2 (gelatinase A) regulates glomerular mesangial cell proliferation and differentiation. J Am Soc Biochem Molecular Biol 1996; 271 (25): 15074-15083.Turk J., Pollock A.S., Lee L.K et al. Matrix metalloproteinase 2 (gelatinase A) regulates glomerular mesangial cell proliferation and differentiation. J Am Soc Biochem Molecular Biol 1996; 271 (25): 15074-15083.Uchio K., Manabe N., Tamura K. et al. Decreased matrix metalloproteinases activity in the kidney of hereditary nephrotic mice (ICGN strain). Nephron 2000; 86: 145-151.Uchio K., Manabe N., Tamura K. et al. Decreased matrix metalloproteinases activity in the kidney of hereditary nephrotic mice (ICGN strain). Nephron 2000; 86: 145-151.Visse R., Nagase H. Matrix metalloproteinases and tissue inhibitors of metalloproteinases: structure, function and biochemistry. Circ Res 2003; 92: 827-839.Visse R., Nagase H. Matrix metalloproteinases and tissue inhibitors of metalloproteinases: structure, function and biochemistry. Circ Res 2003; 92: 827-839.Wojtovicz-Praga S.M., Dickson R.M., Hawkins M.J. et al. Matrix metalloproteinases inhibitors. Invest New Drugs 1997; 15: 61-75.Wojtovicz-Praga S.M., Dickson R.M., Hawkins M.J. et al. Matrix metalloproteinases inhibitors. Invest New Drugs 1997; 15: 61-75.Wolf G. Angiotensin II: a pivotal factor in the progression of renal diseases. Nephrol Dial Transplant 1999; 14 (1): 41-44.Wolf G. Angiotensin II: a pivotal factor in the progression of renal diseases. Nephrol Dial Transplant 1999; 14 (1): 41-44.

The authors declare that there are no conflicts of interest present.