Abstract
Basic fibroblast growth factor (bFGF or FGF-2) is a pleiotropic growth factor that promotes growth of mesenchymal and epithelial cells, stimulates angiogenesis and neuroprotection. Moreover, exogenous bFGF by stimulating angiogenesis promotes healing of gastroduodenal ulcers and cardiac and brain injury. All these actions were demonstrated in regard to 18kDa bFGF isoform that is secreted by cells via an ER/Golgi-independent pathway and activates FGF receptors. However in some transformed and stressed cells and in some tissues (e.g. brain) the single copy bFGF gene encodes multiple gene products: 18kDa and also higher molecular weight (HMW) bFGF isoforms: ∼21 and ∼22kDa in rodents, and ∼22, ∼23 and ∼24kDa in humans. The biologic roles of these HMW bFGF isoforms in vivo remain unknown. In this study we demonstrated that in normal, uninjured gastric mucosa, bFGF is almost exclusively expressed as 18kDa isoform translated through a classical AUG (methionine) codon. In contrast, in injured gastric mucosa of rat, bFGF gene is preferentially translated to HMW bFGF isoforms through alternative CUG (leucine) initiation codon. Gastric mucosal injury caused in rats a significant increase in bFGF mRNA at 8 and 24h vs. normal mucosa and a significant increase in bFGF protein at 24–72h, mainly due to increased expression of ∼21 and ∼22kDa HMW bFGF isoforms. This is first demonstration that gastric mucosal injury and repair triggers local activation of bFGF gene with preferential translation of HMW bFGF isoforms through a non-canonical CUG codon. This study uncovered CUG-initiated HMW bFGF translation as a novel regulatory mechanism operating in vivo during gastric injury repair.
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
More From: Biochemical and Biophysical Research Communications
Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.