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Soluble betaglycan reduces renal damage progression in db/db mice

¹Departamento de Biología Celular, Instituto de Fisiología Celular, Universidad Nacional Autónoma de México, ²Departamento de Patología, Instituto Nacional de Ciencias Médicas y Nutrición "Salvador Zubirán," and ³Unidad de Fisiología Molecular, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, and Instituto Nacional de Ciencias Médicas y Nutrición "Salvador Zubirán," México City, México

Submitted 13 July 2006 ; accepted in final form 28 August 2006

Transforming growth factor- (TGF-) is a key mediator in the pathogenesis of renal diseases. Betaglycan, also known as the type III TGF- receptor, regulates TGF- action by modulating its access to the type I and II receptors. Betaglycan potentiates TGF-; however, soluble betaglycan, which is produced by the shedding of the membrane-bound receptor, is a potent antagonist of TGF-. In the present work, we have used a recombinant form of soluble betaglycan (SBG) to prevent renal damage in genetically obese and diabetic db/db mice. Eight-wk-old db/db or nondiabetic (db/m) mice were injected intraperitoneally with 50 µg of SBG or vehicle alone three times a wk for 8 wk. The db/db mice that received vehicle presented albuminuria and increased serum creatinine, as well as glomerular mesangial matrix expansion. The db/db mice treated with SBG exhibited a reduction in serum creatinine, albuminuria, and structural renal damage. These effects were associated with lower kidney levels of mRNAs encoding TGF-1, TGF-2, TGF-3, collagen IV, collagen I, fibronectin, and serum glucocorticoid kinase as well as a reduction in the immunostaining of collagen IV and fibronectin. Our data indicate that SBG is a renoprotective agent that neutralized TGF- actions in this model of nephropathy. Because SBG has a high affinity for all TGF- isoforms, in particular TGF-2, it is found naturally in serum and tissues and its shedding may be regulated. We believe that SBG shall prove convenient for long-term treatment of kidney diseases and other pathologies in which TGF- plays a pathophysiological role.

diabetic nephropathy; transforming growth factor-; serum glucocorticoid kinase; fibronectin; collagen IV; mesangial matrix expansion

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