1Affiliated with the David R. Bloom Center for Pharmacy at The Hebrew University of Jerusalem.
The pro-fibrogenic effect of nerve growth factor on conjunctival fibroblasts is mediated by transforming growth factor-β
Article first published online: 17 MAY 2005
Clinical & Experimental Allergy
Volume 35, Issue 5, pages 650–656, May 2005
How to Cite
Micera, A., Puxeddu, I., Lambiase, A., Antonelli, A., Bonini, S., Bonini, S., Aloe, L., Pe'er, J. and Levi-Schaffer, F. (2005), The pro-fibrogenic effect of nerve growth factor on conjunctival fibroblasts is mediated by transforming growth factor-β. Clinical & Experimental Allergy, 35: 650–656. doi: 10.1111/j.1365-2222.2005.02241.x
- Issue published online: 17 MAY 2005
- Article first published online: 17 MAY 2005
- Submitted 16 September 2004; revised 25 January 2005; accepted 21 February 2005
- nerve growth factor;
- tissue remodelling;
- wound healing
Background Nerve growth factor (NGF) and nerve growth factor receptor (NGFR) expressions have been found to be increased in sub-conjunctival scarring.
Objective The aim of this study was to investigate the in vitro effects of NGF on some pro-fibrogenic properties of human conjunctival fibroblasts.
Methods Expression of NGF, trkANGFR and p75NTR on human fibroblasts grown from conjunctival biopsies and incubated for 2 or 6 days with NGF were evaluated by immunofluorescence, RT-PCR, flow cytometry and ELISA. The fibrogenic effect of NGF on conjunctival fibroblasts was investigated by evaluating their migration (wound model), proliferation ([3H]-thymidine incorporation), collagen production (3H]-proline incorporation), expression of alpha-smooth muscle actin (α-SMA) (cell surface ELISA) and contraction of 3D collagen gels.
Results NGF induced the expression of p75NTR in the fibroblasts that constitutively expressed only trkANGF and increased the migration of wounded fibroblasts, but not their proliferation and collagen production. NGF induced the conversion of fibroblasts into myofibroblasts expressing α-SMA, and enhanced their contraction of a collagen matrix. Interestingly, chronic NGF treatment induced transforming growth factor-β1 (TGF-β1) production by fibroblasts, and following specific TGF-β neutralization, all the NGF-induced effects were completely abrogated.
Conclusion Our findings indicate that NGF, via TGF-β induction, is likely to be involved in the healing or fibrotic processes occurring in conjunctiva during some pathological conditions.