Fibroblast growth factor 2 decreases bleomycin‐induced pulmonary fibrosis and inhibits fibroblast collagen production and myofibroblast differentiation

• DOI: 10.1002/path.5106
• Publication Date: 2018-06-06T09:30:33Z
• Authors: Hyun Young Koo; Lamis MF El‐Baz; StaceyL House; Sarah N Cilvik; Samuel J Dorry; Nahla M Shoukry; Mohamed L Salem; Hani S Hafez; Nickolai O Dulin; David M Ornitz; Robert D Guzy
• Keywords: Myofibroblast

Abstract Fibroblast growth factor (FGF) signaling has been implicated in the pathogenesis of pulmonary fibrosis. Mice lacking FGF2 have increased mortality and impaired epithelial recovery after bleomycin exposure, supporting a protective or reparative function following lung injury. To determine whether overexpression reduces bleomycin‐induced injury, we developed an inducible genetic system to express type II pneumocytes. Double‐transgenic (DTG) mice with doxycycline‐inducible human ( SPC‐rtTA;TRE‐hFGF2 ) single‐transgenic controls were administered intratracheal fed doxycycline chow, starting at either day 0 7. In addition, wild‐type received intravenous recombinant FGF2, time treatment. Compared controls, doxycycline‐induced DTG had decreased fibrosis 21 days bleomycin, as assessed by gene expression histology. This beneficial effect was seen when induced 7 bleomycin. did not alter expression, bronchoalveolar lavage cellularity total protein. vitro studies using primary mouse fibroblasts showed that strongly inhibited baseline TGFβ1‐induced alpha smooth muscle actin (αSMA), collagen, connective tissue factor. While suppress phosphorylation Smad2 Smad‐dependent stress fiber formation serum response factor‐dependent expression. inhibition αSMA requires FGF receptor 1 (FGFR1) downstream MEK/ERK, but AKT signaling. summary, protects against vivo reverses collagen , without affecting inflammation Our results suggest lung, is antifibrotic part through fibroblast myofibroblast differentiation. Copyright © 2018 Pathological Society Great Britain Ireland. Published John Wiley & Sons, Ltd.