Endostatin and Transglutaminase 2 are Involved in Fibrosis of the Aging Kidney
Biochemistry and Molecular Biology
Endostatin (EST), an antiangiogenic factor, is enriched in aging kidneys. EST is also an interactive partner of transglutaminase 2 (TG2), an enzyme that cross-links extracellular matrix proteins. Here we tested whether EST and TG2 play a role in the fibrosis of aging. In wild-type mice, aging kidneys exhibited a 2- to 4-fold increase in TG2 paralleled by increased cross-linked extracellular matrix proteins and fibrosis. Mice transgenic to express EST showed renal fibrosis at a young age. One-month delivery of EST via minipumps to young mice showed increased renal fibrosis that became more robust when superimposed on folic acid-induced nephropathy. Upregulated TG2 and impaired renal function were apparent with EST delivery combined with folic acid-induced nephropathy. Subcapsular injection of TG2 and/or EST into kidneys of young mice not only induced interstitial fibrosis, but also increased the proportion of senescent cells. Thus, kidney fibrosis in aging may represent a natural outcome of upregulated EST and TG2, but more likely it appears to be a result of cumulative stresses occurring on the background of synergistically acting geronic (aging) proteins, EST and TG2.
Lin, C. H., Chen, J., Zhang, Z., Johnson, G. V., Cooper, A. J., Feola, J., . . . Goligorsky, M. S. (2016). Endostatin and transglutaminase 2 are involved in fibrosis of the aging kidney. Kidney International, 89(6), 1281-1292. doi:10.1016/j.kint.2016.01.030
Originally published in Kidney International. https://doi.org/10.1016/j.kint.2016.01.030