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Lopez-Casillas, F; Juarez, P; Vilchis-Landeros, MM; Ponce-Coria, J; Mendoza, V; Hernandez-Pando, R; Bobadilla, NA (2007)


AM J PHYSIOL-RENAL 292(1):F321-F329
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Transforming growth factor-beta (TGF-beta) is a key mediator in the pathogenesis of renal diseases. Betaglycan, also known as the type III TGF-beta receptor, regulates TGF-beta action by modulating its access to the type I and II receptors. Betaglycan potentiates TGF-beta; however, soluble betaglycan, which is produced by the shedding of the membrane-bound receptor, is a potent antagonist of TGF-beta. 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 mu g 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-beta 1, TGF-beta 2, TGF-beta 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-beta actions in this model of nephropathy. Because SBG has a high affinity for all TGF-beta isoforms, in particular TGF-beta 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-beta plays a pathophysiological role.