chronic nerve growth factor exposure increases apoptosis in a model of in vitro induced conjunctival myofibroblasts慢性神经生长因子暴露增加细胞凋亡在体外诱导结膜myofibroblasts的典范.pdfVIP

Chronic Nerve Growth Factor Exposure Increases Apoptosis in a Model of In Vitro Induced Conjunctival Myofibroblasts 1 2 1 3 Alessandra Micera , Ilaria Puxeddu , Bijorn Omar Balzamino , Stefano Bonini , Francesca Levi- Schaffer2* 1 IRCCS - G.B. Bietti Foundation, Rome, Italy, 2 Department of Pharmacology and Experimental Therapeutics, School of Pharmacy, Institute for Drug Research, Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem, Israel, 3 Department of Ophthalmology, University Campus Bio-Medico, Rome, Italy Abstract In the conjunctiva, repeated or prolonged exposure to injury leads to tissue remodeling and fibrosis associated with dryness, lost of corneal transparency and defect of ocular function. At the site of injury, fibroblasts (FB) migrate and differentiate into myofibroblasts (myoFB), contributing to the healing process together with other cell types, cytokines and growth factors. While the physiological deletion of MyoFB is necessary to successfully end the healing process, myoFB prolonged survival characterizes the pathological process of fibrosis. The reason for myoFB persistence is poorly understood. Nerve Growth Factor (NGF), often increased in inflamed stromal conjunctiva, may represent an important molecule both in many inflammatory processes characterized by tissue remodeling and in promoting wound-healing and well-balanced repair in humans. NGF effects are mediated by the specific expression of the NGF neurotrophic tyrosine kinase receptor type 1 (trkANGFR) and/or the pan-neurotrophin glycoprotein receptor (p75NTR). Therefore, a conjunctival myoFB model (TGFb1-induced myoFB) was developed and characterized f