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Evidence for a role of transforming growth factor (TGF)-beta1 in the induction of postglomerular albuminuria in diabetic nephropathy: amelioration by soluble TGF-beta type II receptor.
Diabetes. 2007 Feb; 56(2):380-8.D

Abstract

Transforming growth factor-beta (TGF-beta) has previously been implicated in the progression of diabetic nephropathy, including the onset of fibrosis and albuminuria. Here we report for the first time the use of a high-affinity TGF-beta1 binding molecule, the soluble human TGF-beta type II receptor (sTbetaRII.Fc), in the treatment of diabetic nephropathy in 12-week streptozotocin-induced diabetic Sprague-Dawley rats. In vitro studies using immortalized rat proximal tubule cells revealed that 50 pmol/l TGF-beta1 disrupted albumin uptake (P < 0.001 vs. control), an inhibition significantly reversed by the use of the sTbetaRII.Fc (1,200 pmol/l). In vivo studies demonstrated that treatment with sTbetaRII.Fc reduced urinary albumin excretion by 36% at 4 weeks, 59% at 8 weeks (P < 0.001), and 45% at 12 weeks (P < 0.01 for diabetic vs. treated). This was correlated with an increase in megalin expression (P < 0.05 for diabetic vs. treated) and a reduction in collagen IV expression following sTbetaRII.Fc treatment (P < 0.001 for diabetic vs. treated). These changes occurred independently of changes in blood glucose levels. This study demonstrates that the sTbetaRII.Fc is a potential new agent for the treatment of fibrosis and albuminuria in diabetic nephropathy and may reduce albuminuria by reducing TGF-beta1-induced disruptions of renal proximal tubule cell uptake of albumin.

Authors+Show Affiliations

Program in Membrane Biology, Division of Nephrology, Department of Medicine, Massachusetts General Hospital/Harvard Medical School, Simches Research Center, 185 Cambridge Street, Boston, MA 02114, USA. leileata.russo@receptor.mgh.harvard.eduNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

17259382

Citation

Russo, Leileata M., et al. "Evidence for a Role of Transforming Growth Factor (TGF)-beta1 in the Induction of Postglomerular Albuminuria in Diabetic Nephropathy: Amelioration By Soluble TGF-beta Type II Receptor." Diabetes, vol. 56, no. 2, 2007, pp. 380-8.
Russo LM, del Re E, Brown D, et al. Evidence for a role of transforming growth factor (TGF)-beta1 in the induction of postglomerular albuminuria in diabetic nephropathy: amelioration by soluble TGF-beta type II receptor. Diabetes. 2007;56(2):380-8.
Russo, L. M., del Re, E., Brown, D., & Lin, H. Y. (2007). Evidence for a role of transforming growth factor (TGF)-beta1 in the induction of postglomerular albuminuria in diabetic nephropathy: amelioration by soluble TGF-beta type II receptor. Diabetes, 56(2), 380-8.
Russo LM, et al. Evidence for a Role of Transforming Growth Factor (TGF)-beta1 in the Induction of Postglomerular Albuminuria in Diabetic Nephropathy: Amelioration By Soluble TGF-beta Type II Receptor. Diabetes. 2007;56(2):380-8. PubMed PMID: 17259382.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Evidence for a role of transforming growth factor (TGF)-beta1 in the induction of postglomerular albuminuria in diabetic nephropathy: amelioration by soluble TGF-beta type II receptor. AU - Russo,Leileata M, AU - del Re,Elisabetta, AU - Brown,Dennis, AU - Lin,Herbert Y, PY - 2007/1/30/pubmed PY - 2007/4/10/medline PY - 2007/1/30/entrez SP - 380 EP - 8 JF - Diabetes JO - Diabetes VL - 56 IS - 2 N2 - Transforming growth factor-beta (TGF-beta) has previously been implicated in the progression of diabetic nephropathy, including the onset of fibrosis and albuminuria. Here we report for the first time the use of a high-affinity TGF-beta1 binding molecule, the soluble human TGF-beta type II receptor (sTbetaRII.Fc), in the treatment of diabetic nephropathy in 12-week streptozotocin-induced diabetic Sprague-Dawley rats. In vitro studies using immortalized rat proximal tubule cells revealed that 50 pmol/l TGF-beta1 disrupted albumin uptake (P < 0.001 vs. control), an inhibition significantly reversed by the use of the sTbetaRII.Fc (1,200 pmol/l). In vivo studies demonstrated that treatment with sTbetaRII.Fc reduced urinary albumin excretion by 36% at 4 weeks, 59% at 8 weeks (P < 0.001), and 45% at 12 weeks (P < 0.01 for diabetic vs. treated). This was correlated with an increase in megalin expression (P < 0.05 for diabetic vs. treated) and a reduction in collagen IV expression following sTbetaRII.Fc treatment (P < 0.001 for diabetic vs. treated). These changes occurred independently of changes in blood glucose levels. This study demonstrates that the sTbetaRII.Fc is a potential new agent for the treatment of fibrosis and albuminuria in diabetic nephropathy and may reduce albuminuria by reducing TGF-beta1-induced disruptions of renal proximal tubule cell uptake of albumin. SN - 0012-1797 UR - https://www.unboundmedicine.com/medline/citation/17259382/Evidence_for_a_role_of_transforming_growth_factor__TGF__beta1_in_the_induction_of_postglomerular_albuminuria_in_diabetic_nephropathy:_amelioration_by_soluble_TGF_beta_type_II_receptor_ L2 - https://diabetes.diabetesjournals.org/lookup/pmidlookup?view=long&amp;pmid=17259382 DB - PRIME DP - Unbound Medicine ER -