We studied modulation of the expression of extracellular matrix proteins under conditions of meprin inhibition in rats with LPS-induced endotoxemia. Endotoxemia increased the expression of type I, III, IV collagens and fibronectin in the renal tissue and type III and IV collagens in the heart. Meprin inhibitor actinonin reduced expression of both meprins and genes of extracellular matrix proteins, but the intensity of this effect in the heart and kidney was different. Inhibition of meprins in endotoxemia can prevent pathological remodeling of the extracellular matrix in the heart and kidney.
Similar content being viewed by others
References
Bonnans C, Chou J, Werb Z. Remodelling the extracellular matrix in development and disease. Nat. Rev. Mol. Cell. Biol. 2014;15(12):786-801. doi: https://doi.org/10.1038/nrm3904
Brower GL, Gardner JD, Forman MF, Murray DB, Voloshenyuk T, Levick SP, Janicki JS. The relationship between myocardial extracellular matrix remodeling and ventricular function. Eur. J. Cardiothorac. Surg. 2006;30(4):604-610. doi: https://doi.org/10.1016/j.ejcts.2006.07.006
Bylander JE, Ahmed F, Conley SM, Mwiza JM, Ongeri EM. Meprin Metalloprotease Deficiency Associated with Higher Mortality Rates and More Severe Diabetic Kidney Injury in Mice with STZ-Induced Type 1 Diabetes. J. Diabetes Res. 2017;2017:9035038. doi: https://doi.org/10.1155/2017/9035038
Bylander J, Li Q, Ramesh G, Zhang B, Reeves WB, Bond JS. Targeted disruption of the meprin metalloproteinase beta gene protects against renal ischemia-reperfusion injury in mice. Am. J. Physiol. Renal Physiol. 2008;294(3):F480-F490. doi: https://doi.org/10.1152/ajprenal.00214.2007
Cohen AH. Collagen Type III Glomerulopathies. Adv. Chronic. Kidney Dis. 2012;19(2):101-106. doi: https://doi.org/10.1053/j.ackd.2012.02.017
van Dijk A, Niessen HW, Ursem W, Twisk JW, Visser FC, van Milligen FJ. Accumulation of fibronectin in the heart after myocardial infarction: a putative stimulator of adhesion and proliferation of adipose-derived stem cells. Cell. Tissue Res. 2008;332(2):289-298. doi: https://doi.org/10.1007/s00441-008-0573-0
Frangogiannis NG. The Extracellular Matrix in Ischemic and Nonischemic Heart Failure. Circ. Res. 2019;125(1):117-146. doi: https://doi.org/10.1161/CIRCRESAHA.119.311148
Genovese F, Manresa AA, Leeming DJ, Karsdal MA, Boor P. The extracellular matrix in the kidney: a source of novel noninvasive biomarkers of kidney fibrosis? Fibrogenesis Tissue Repair. 2014;7(1):4. doi: https://doi.org/10.1186/1755-1536-7-4
Holly MK, Dear JW, Hu X, Schechter AN, Gladwin MT, Hewitt SM, Yuen PS, Star RA. Biomarker and drug-target discovery using proteomics in a new rat model of sepsis-induced acute renal failure. Kidney Int. 2006;70(3):496-506. doi: https://doi.org/10.1038/sj.ki.5001575
Jefferson T, Auf dem Keller U, Bellac C, Metz VV, Broder C, Hedrich J, Ohler A, Maier W, Magdolen V, Sterchi E, Bond JS, Jayakumar A, Traupe H, Chalaris A, Rose-John S, Pietrzik CU, Postina R, Overall CM, Becker-Pauly C. The substrate degradome of meprin metalloproteases reveals an unexpected proteolytic link between meprin β and ADAM10. Cell. Mol. Life Sci. 2013;70(2):309-333. doi: https://doi.org/10.1007/s00018-012-1106-2
Kim HE, Dalal SS, Young E, Legato MJ, Weisfeldt ML, D’Armiento J. Disruption of the myocardial extracellular matrix leads to cardiac dysfunction. J. Clin. Invest. 2000;106(7):857- 866. doi: 10.1172/JCI8040
Kong P, Christia P, Frangogiannis NG. The pathogenesis of cardiac fibrosis. Cell. Mol. Life Sci. 2014;71(4):549-574. doi: https://doi.org/10.1007/s00018-013-1349-6
Negri AL. Prevention of progressive fibrosis in chronic renal diseases: antifibrotic agents. J. Nephrol. 2004;17(4):496-503.
Yura RE, Bradley SG, Ramesh G, Reeves WB, Bond JS. Meprin A metalloproteases enhance renal damage and bladder inflammation after LPS challenge. Am. J. Physiol. Renal. Physiol. 2009;296(1):F135-F144. doi: https://doi.org/10.1152/ajprenal.90524.2008
Zhang S, Xu L, Liang R, Yang C, Wang P. Baicalin suppresses renal fibrosis through microRNA-124/TLR4/NF-κB axis in streptozotocin-induced diabetic nephropathy mice and high glucose-treated human proximal tubule epithelial cells. J. Physiol. Biochem. 2020;76(3):407-416. doi: https://doi.org/10.1007/s13105-020-00747-z
Author information
Authors and Affiliations
Corresponding author
Additional information
Translated from Byulleten’ Eksperimental’noi Biologii i Meditsiny, Vol. 170, No. 12, pp. 729-733, December, 2020
Rights and permissions
About this article
Cite this article
Chepurnova, D.A., Samoilova, E.V., Fesenko, А.G. et al. Reduced Expression of Extracellular Matrix Proteins in the Heart and Kidneys of Rats with Endotoxemia under the Effect of Actinonin. Bull Exp Biol Med 170, 744–747 (2021). https://doi.org/10.1007/s10517-021-05146-y
Received:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s10517-021-05146-y