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1 Instituto de Fisiología Celular, Universidad Nacional Autonoma de México, Mexico, Distrito Federal, Mexico
2 Instituto de Fisiología Celular, Universidad Nacional Autonoma de México, México, Distrito Federal, Mexico
3 Departamento de, Instituto Nacional de Ciencias Médicas y Nutrición "Salvador Zubirán", México, Distrito Federal, Mexico
4 Molecular Physiology Unit, Instituto de Investigaciones Biomédicas, UNAM and Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, México, Distrito Federal, Mexico
5 Instituto de Fisiología Celular, Universidad Nacional Autónoma de México, Mexico, DF, Mexico
* To whom correspondence should be addressed. E-mail: fcasilla{at}ifc.unam.mx.
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 the genetically obese and diabetic db/db mice. Eight-week-old diabetic (db/db) or non-diabetic (db/m) mice were injected intraperitoneally with 50 µg of SBG or vehicle alone, three times per week during 8 weeks. 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 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 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 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.
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