M. Ohji et al., TRANSFORMING GROWTH-FACTOR-BETA STIMULATES COLLAGEN AND FIBRONECTIN SYNTHESIS BY HUMAN CORNEAL STROMAL FIBROBLASTS IN-VITRO, Current eye research, 12(8), 1993, pp. 703-709
The effects of transforming growth factor-beta (TGFbeta) and epidermal
growth factor (EGF) on the synthesis of collagen and fibronectin, and
on the proliferation of human corneal stromal fibroblasts in vitro, w
ere evaluated. Human corneal stromal fibroblasts in culture were incub
ated for 48 hours with TGFbeta or EGF in the absence of serum. Collage
n and fibronectin in the culture media were measured by a collagenase-
digestion assay and a competitive ELISA, respectively. The effects of
the growth factors on proliferation were assessed by H-3-thymidine inc
orporation. Collagen synthesis was dose-dependently stimulated by TGFb
eta; at a concentration of 1 ng/ml of TGFbeta, a 120% increase in coll
agen synthesis was seen over that of controls (p<0.01). EGF, at a conc
entration of 10 ng/ml, induced a 40% increase in collagen synthesis ov
er that of controls (p<0.01). The maximum stimulation by TGFbeta was g
reater than that by EGF (p<0.05). Fibronectin synthesis was stimulated
by TGFbeta and EGF in a dose-dependent manner; 230% (p<0.001) and 210
% (p<0.01) increases in fibronectin synthesis were caused by 10 ng/ml
TGFbeta and EGF, respectively. TGFbeta and EGF dose-dependently stimul
ated H-3-thymidine incorporation. The maximum increases in H-3-thymidi
ne incorporation reached 180% (p<0.001) and 190% (p<0.001) over that i
n controls, at 10 ng/ml concentrations of TGFbeta and EGF, respectivel
y. In conclusion, both TGFbeta and EGF are potent stimulants of collag
en and fibronectin synthesis and proliferation. Therefore, these two g
rowth factors may be effective alternatives or additional choices for
the treatment of corneal ulcer.