Soluble betaglycan reduces renal damage progression in db/db mice.
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 mug 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-beta1, TGF-beta2, TGF-beta3, 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-beta2, 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.
Juárez
Patricia
P
Departamento de Biología Celular, Instituto de Fisiología Celular, Universidad Nacional Autónoma de México.
Vilchis-Landeros
M Magdalena
MM
Ponce-Coria
José
J
Mendoza
Valentín
V
Hernández-Pando
Rogelio
R
Bobadilla
Norma A
NA
López-Casillas
Fernando
F
D000419:Albuminuria / Q000652:urine; D000818:Animals; D003094:Collagen / Q000096:biosynthesis; D003404:Creatinine / Q000097:blood; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy / Q000235:genetics; D018450:Disease Progression; D015536:Down-Regulation / Q000187:drug effects; D005353:Fibronectins / Q000378:metabolism; D005920:Glomerular Mesangium / Q000473:pathology; D007150:Immunohistochemistry; D007674:Kidney Diseases / Q000139:chemically induced* / Q000235:genetics / Q000473:pathology*; D007678:Kidney Glomerulus / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D011134:Polysaccharides / Q000627:therapeutic use*; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014018:Tissue Distribution; D016212:Transforming Growth Factor beta / Q000037:antagonists & inhibitors
D005353:Fibronectins; D011134:Polysaccharides; D012333:RNA, Messenger; D016212:Transforming Growth Factor beta; D003094:Collagen; D003404:Creatinine