Overexpression of transforming growth factor-beta 1 mRNA is associated with up-regulation of glomerular tenascin and laminin gene expression in nonobese diabetic mice.
Nonobese diabetic (NOD) mice spontaneously develop immune-mediated insulin-dependent diabetes mellitus and nephropathy, providing an opportunity to study the early molecular events in a model of diabetic glomerulosclerosis. The expression of several genes coding for growth factors and extracellular matrix was examined in microdissected glomeruli, by the use of reverse transcription-competitive polymerase chain reaction, in diabetic NOD mice (mean duration of diabetes, 28.5 +/- 7 days) and age-matched nondiabetic NOD mice with normal glucose tolerance. The levels of mRNA coding for transforming growth factor-beta 1, tenascin, and laminin B1 increased 1.9-, 2.0-, and 1.7-fold, respectively, whereas platelet-derived growth factor (PDGF)-B, alpha 1(IV) collagen, 72-kd collagenase, alpha-smooth muscle actin, and beta-actin mRNA remained stable in the diabetic mice. The kidney advanced glycosylation end-products levels increased 2.1-fold in the diabetic mice, and the diabetic glomeruli showed an accumulation of tenascin and laminin but not of type IV collagen by immunofluorescence microscopy. There was no increase in cell number per glomerulus after the onset of diabetes, a finding consistent with stable PDGF-B and alpha-smooth muscle actin mRNA levels. These findings provide evidence that increased glomerular transforming growth factor-beta 1, but not PDGF-B, mRNA is associated with the up-regulation of tenascin and laminin expression after advanced glycosylation endproduct accumulation, early after the onset of diabetes.
Yang
C W
CW
Renal Cell Biology Section, National Institute of Diabetes, Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
Hattori
M
M
Vlassara
H
H
He
C J
CJ
Carome
M A
MA
Yamato
E
E
Elliot
S
S
Striker
G E
GE
Striker
L J
LJ
D000818:Animals; D001483:Base Sequence; D015816:Cell Adhesion Molecules, Neuronal / Q000235:genetics*; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics* / Q000473:pathology; D016326:Extracellular Matrix Proteins / Q000235:genetics*; D005260:Female; D015870:Gene Expression; D007678:Kidney Glomerulus / Q000473:pathology / Q000503:physiopathology*; D007797:Laminin / Q000235:genetics*; D051379:Mice; D016688:Mice, Inbred NOD / Q000235:genetics; D008856:Microscopy, Fluorescence; D015335:Molecular Probes / Q000235:genetics; D008969:Molecular Sequence Data; D012333:RNA, Messenger / Q000378:metabolism*; D019063:Tenascin; D016212:Transforming Growth Factor beta / Q000235:genetics*
D015816:Cell Adhesion Molecules, Neuronal; D016326:Extracellular Matrix Proteins; D007797:Laminin; D015335:Molecular Probes; D012333:RNA, Messenger; D019063:Tenascin; D016212:Transforming Growth Factor beta