Cellular and molecular effects of fibroblast growth factors 2 and 4 on human umbilical veinal endothelial cells

Abstract

Fibroblast growth factors (FGFs), encompasses a family of 22 related polypeptide. There are 18 different biologically active FGF proteins. They influence a wide array of biological and physiological responses such as migration, proliferation, tissue homeostasis, and wound healing. Most FGF are secreted and bind to heparin sulphate binding proteins (HPSG) in the extra cellular matrix (ECM). FGF-binding protein (FGF-BP) is a chaperon protein that binds to FGF releasing from the ECM and chaperoning it to bind to FGF receptors (FGFRs). FGFR dimerize when bound to FGF and starts series of a signal cascade that ultimately leads to the activation of MAPK. FGF2 and FGF4 are selected from the pool of 18 different FGF to be studied in this investigation. Both FGF2 and FGF4 have been reported to be critical for development during embryogenesis. De-regulation of these proteins could lead to various pathologies including different types of cancers. Hence we attempt to investigate the cellular and molecular role of these proteins and their implication on cells in an attempt to set up a foundational understanding for further studies that will include FGF-BPs and FGFRs. To do so, we used HUVECs to examine FGF2 and FGF4 activity through Western Blot analysis. We also investigated their effect on migration using the ECIS Migration Assays, on wound healing by the ECIS Wound Healing Assays and captured wound healing images through Incucyte. Data from these experiments indicated that both, FGF2 and FGF4, have a role in cellular migration and wound healing. They also show they have a dose response on these cells. As a result, we can use these models to further investigate FGF2 and FGF4 modulation by FGF-BP1 and FGF-BP3 and the affects cellular response.