Expression of transforming growth factor-beta and type IV collagen in early streptozotocin-induced diabetes

The role of transforming growth factor-beta (TGF-beta) in restitution was examined in intact sheets of injured guinea pig gastric mucosa in which the epithelial cell-collagen interaction can be quantitatively evaluated. The luminal surface of intact sheets of in vitro guinea pig gastric mucosa was injured by exposure to 1.25 mol/l NaCl for 10 min. Restitution was evaluated by measurement of transmucosal electrical resistance and [3H]mannitol flux before and after injury. Recovery of electrical resistance and [3H]mannitol flux was retarded by inhibition of endogenous TGF-beta with either aprotinin or anti-TGF-beta antibody; effects were restored by human recombinant TGF-beta1. During inhibition of endogenous TGF-beta, type IV collagen accelerated the recovery. Inhibition of reconstruction of the basement membrane by simultaneous addition of cis-4-OH-L-proline and anti-type IV collagen completely abolished the enhancement of the recovery by TGF-beta 1. These results suggest that endogenous TGF-beta is required for restitution to occur in guinea pig gastric mucosa and that type IV collagen plays an important role in TGF-beta-abetted restitution.

Download Full-text

Experimental bilateral urinary obstruction in fetal sheep: transforming growth factor-beta 1 expression

AJP Renal Physiology ◽

10.1152/ajprenal.1997.273.3.f372 ◽

1997 ◽

Vol 273 (3) ◽

pp. F372-F379 ◽

Cited By ~ 5

Author(s):

A. A. Medjebeur ◽

L. Bussieres ◽

B. Gasser ◽

V. Gimonet ◽

K. Laborde

Keyword(s):

Growth Factor ◽

Transforming Growth Factor Beta ◽

Transforming Growth Factor ◽

Urinary Obstruction ◽

Urinary Concentration ◽

Tgf Beta ◽

Fetal Sheep ◽

Type Iv ◽

Growth Factor Beta

To gain insight into the role of transforming growth factor-beta 1 (TGF-beta 1) in the development of kidney pathology following fetal obstruction, we measured TGF-beta 1 gene expression, the active peptide, and the urinary concentration in a model of fetal bilateral urinary obstruction (BUO) in sheep. Fetal lambs underwent BUO at 60 (FO-60) or 80 days (FO-80) of gestation and were studied at 120 days. Independently of the onset or duration of obstruction, all fetuses developed type IV dysplasia (IV) associated with an arrest in the nephrogenesis or hydronephrosis. Fetal glomerular filtration rate was not significantly modified, whereas sodium tubular reabsorption was significantly decreased, and urinary TGF-beta 1 concentration was elevated in hydronephrosis but not in IV. Levels of TGF-beta 1 mRNA were increased in hydronephrosis compared with normal kidneys, and active TGF-beta 1 immunoreactivity was increased in both hydronephrotic and IV kidneys. In summary, TGF-beta 1 may play a role in the development of hydronephrosis and dysplasia in kidneys following fetal BUO. Its role in the arrest of nephrogenesis observed in the IV kidneys remains to be proved.

Download Full-text

Molecular analysis of spontaneous glomerulosclerosis in Os/+ mice, a model with reduced nephron mass

AJP Renal Physiology ◽

10.1152/ajprenal.1995.269.2.f266 ◽

1995 ◽

Vol 269 (2) ◽

pp. F266-F273 ◽

Cited By ~ 1

Author(s):

C. He ◽

R. K. Zalups ◽

D. A. Henderson ◽

G. E. Striker ◽

L. J. Striker

Keyword(s):

Growth Factor ◽

Transforming Growth Factor Beta ◽

Type Iv Collagen ◽

Transforming Growth Factor ◽

Cell Number ◽

Mrna Levels ◽

Electron Microscopic ◽

Type Iv ◽

Electron Microscopic Morphometry ◽

Glomerular Size

Oligosyndactyly mice (ROP Os/+) are a radiation-induced mutant strain with reduced glomerular number and increased glomerular size. We found that they develop glomerulosclerosis. At 3 mo, ROP Os/+ mice had diffuse mesangial expansion by light microscopy, whereas their +/+ littermates did not. Electron microscopic morphometry revealed a twofold increase in mesangial areas but no changes in the thickness of glomerular basal laminae. Mean glomerular volume was increased 1.8-fold. Cell number and thymidine labeling index were increased 1.3- and 2.4-fold, respectively. The amount of glomerular type IV collagen and tenascin but not laminin was increased by immunofluorescence microscopy. mRNA levels in microdissected glomeruli were measured by competetive reverse transcription-polymerase chain reaction and corrected for cell number. alpha 1-Chain type IV collagen and tenascin mRNAs were increased 3.2-fold and 1.8-fold, whereas laminin B1 mRNA levels were not. The levels of 72-kDa collagenase mRNA were increased 1.6-fold. Transforming growth factor-beta 1 mRNA levels were elevated 1.8-fold, but platelet-derived growth factor-B mRNA levels remained normal. This is the first analysis of glomerular molecular and cellular changes in a model of congenital nephron reduction.

Download Full-text