Transglutaminase inhibition ameliorates experimental diabetic nephropathy. Export

@article{citeulike:5021966, abstract = {Diabetic nephropathy is characterized by excessive extracellular matrix accumulation resulting in renal scarring and end-stage renal disease. Previous studies have suggested that transglutaminase type 2, by formation of its protein crosslink product epsilon-(gamma-glutamyl)lysine, alters extracellular matrix homeostasis, causing basement membrane thickening and expansion of the mesangium and interstitium. To determine whether transglutaminase inhibition can slow the progression of chronic experimental diabetic nephropathy over an extended treatment period, the inhibitor NTU281 was given to uninephrectomized streptozotocin-induced diabetic rats for up to 8 months. Effective transglutaminase inhibition significantly reversed the increased serum creatinine and albuminuria in the diabetic rats. These improvements were accompanied by a fivefold decrease in glomerulosclerosis and a sixfold reduction in tubulointerstitial scarring. This was associated with reductions in collagen IV accumulation by 4 months, along with reductions in collagens I and III by 8 months. This inhibition also decreased the number of myofibroblasts, suggesting that tissue transglutaminase may play a role in myofibroblast transformation. Our study suggests that transglutaminase inhibition ameliorates the progression of experimental diabetic nephropathy and can be considered for clinical application.}, author = {Huang, Linghong and Haylor, John L. and Hau, Zoe and Jones, Richard A. and Vickers, Melissa E. and Wagner, Bart and Griffin, Martin and Saint, Robert E. and Coutts, Ian G. and El Nahas, A. Meguid and Johnson, Timothy S.}, citeulike-article-id = {5021966}, citeulike-linkout-0 = {http://dx.doi.org/10.1038/ki.2009.230}, citeulike-linkout-1 = {http://dx.doi.org/10.1038/ki2009230a}, citeulike-linkout-2 = {http://view.ncbi.nlm.nih.gov/pubmed/19553913}, citeulike-linkout-3 = {http://www.hubmed.org/display.cgi?uids=19553913}, day = {24}, doi = {10.1038/ki.2009.230}, issn = {1523-1755}, journal = {Kidney international}, keywords = {dn, rat, stz, tgt, unx}, month = {August}, number = {4}, pages = {383--394}, posted-at = {2009-06-30 13:12:12}, priority = {2}, publisher = {Nature Publishing Group}, title = {Transglutaminase inhibition ameliorates experimental diabetic nephropathy.}, url = {http://dx.doi.org/10.1038/ki.2009.230}, volume = {76}, year = {2009} }

TY - JOUR ID - citeulike:5021966 L3 - citeulike-article-id:5021966 N2 - Diabetic nephropathy is characterized by excessive extracellular matrix accumulation resulting in renal scarring and end-stage renal disease. Previous studies have suggested that transglutaminase type 2, by formation of its protein crosslink product epsilon-(gamma-glutamyl)lysine, alters extracellular matrix homeostasis, causing basement membrane thickening and expansion of the mesangium and interstitium. To determine whether transglutaminase inhibition can slow the progression of chronic experimental diabetic nephropathy over an extended treatment period, the inhibitor NTU281 was given to uninephrectomized streptozotocin-induced diabetic rats for up to 8 months. Effective transglutaminase inhibition significantly reversed the increased serum creatinine and albuminuria in the diabetic rats. These improvements were accompanied by a fivefold decrease in glomerulosclerosis and a sixfold reduction in tubulointerstitial scarring. This was associated with reductions in collagen IV accumulation by 4 months, along with reductions in collagens I and III by 8 months. This inhibition also decreased the number of myofibroblasts, suggesting that tissue transglutaminase may play a role in myofibroblast transformation. Our study suggests that transglutaminase inhibition ameliorates the progression of experimental diabetic nephropathy and can be considered for clinical application. IS - 4 JF - Kidney international SN - 1523-1755 EP - 394 TI - Transglutaminase inhibition ameliorates experimental diabetic nephropathy. PB - Nature Publishing Group VL - 76 SP - 383 KW - dn KW - rat KW - stz KW - tgt KW - unx AU - Huang, Linghong AU - Haylor, John AU - Hau, Zoe AU - Jones, Richard AU - Vickers, Melissa AU - Wagner, Bart AU - Griffin, Martin AU - Saint, Robert AU - Coutts, Ian AU - El Nahas, Meguid AU - Johnson, Timothy PY - 2009/08/24/ UR - http://dx.doi.org/10.1038/ki.2009.230 ER -