This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Bolick, D. T. Articles by Nadler, J. L. Search for Related Content PubMed PubMed Citation Articles by Bolick, D. T. Articles by Nadler, J. L.

Lisofylline, a Novel Antiinflammatory Compound, Protects Mesangial Cells from Hyperglycemia- and Angiotensin II-Mediated Extracellular Matrix Deposition

Division of Endocrinology and Metabolism, University of Virginia Medical Center, Charlottesville, Virginia 22908

Address all correspondence and requests for reprints to: Jerry L. Nadler, M.D., Chief, Division of Endocrinology and Metabolism, University of Virginia Medical Center, P.O. Box 801405, 450 Ray C. Hunt Drive, Charlottesville, Virginia 22908-1405. E-mail: jln2n{at}virginia.edu.

Chronic elevated glucose levels and activation of the renal renin-angiotensin system have been implicated in the pathogenesis of diabetic nephropathy. We tested the ability of lisofylline (LSF), a novel antiinflammatory compound, to prevent extracellular matrix (ECM) accumulation and growth factor production by human mesangial cells (HMCs) cultured in chronic elevated glucose (HG) or angiotensin II (AngII). HMCs were cultured in normal glucose (NG) (5.5 mM) and in HG (25 mM) for 7 d or with 10^–7 M AngII for 4 h with or without LSF. Levels of the ECM protein fibronectin and TGF-ß in media were shown to increase in HG compared with NG. LSF decreased HG-induced fibronectin and TGF-ß production to control levels. Increased expression of collagen type IV and laminin was observed in AngII-cultured HMCs. LSF protected HMCs from the AngII induction of these key matrix proteins. cAMP-responsive binding element phosphorylation was significantly higher in both HG and AngII-cultured HMCs. LSF reduced phosphorylation of both cAMP-responsive binding element and p38 MAPK compared with control. These data demonstrate that LSF protects HMCs from HG- and AngII-mediated ECM deposition by the reduction of matrix protein secretion possibly through regulation of TGF-ß production and modulation of the p38 MAPK pathway. These results suggest that LSF may provide therapeutic benefit for prevention or treatment of diabetic nephropathy.

This article has been cited by other articles:

				N. Yano, D. Suzuki, M. Endoh, T. C. Zhao, J. F. Padbury, and Y.-T. Tseng A Novel Phosphoinositide 3-Kinase-dependent Pathway for Angiotensin II/AT-1 Receptor-mediated Induction of Collagen Synthesis in MES-13 Mesangial Cells J. Biol. Chem., June 29, 2007; 282(26): 18819 - 18830. [Abstract] [Full Text] [PDF]