A role for IFITM proteins in angiogenesis

Abstract

The Interferon Inducible Transmembrane (IFITM) proteins were originally identified as part of a multi‐protein complex on the surface of lymphocytes that mediates homotypic adhesion and the transmission of antiproliferative signals. Recently, we have identified the IFITMs as regulators of endothelial cell (EC) sprouting in vitro, and angiogenesis in vivo. Angiogenesis is a multistep process whereby new blood vessels are formed from the preexisting vasculature in response to various angiogenic stimuli. During angiogenesis, EC shift from a quiescent phenotype, to migrating and proliferating cells as they sprout from parent vessels, and back to quiescent cells as the new vessels mature and stabilize. Both IFITM1 and IFITM2 are rapidly induced as EC sprout in vitro and form lumenized vessels, and knockdown of either disrupts both sprouting and lumen formation. Using a vascular bed xeno‐transplant model, we have also identified a role for the human IFITMs during in vivo angiogenesis. Immunohistochemical staining of multiple human tissues identified widespread IFITM expression on vessels. Our data suggest that IFITMs may regulate the transition of EC from a quiescent to an angiogenic state.

Transcriptomic and Functional Evidence That miRNA193a-3p Inhibits Lymphatic Endothelial Cell (LEC) and LEC + MCF-7 Spheroid Growth Directly and by Altering MCF-7 Secretome

“…On one side they directly promote antitumor response by suppressing tumor growth and on the other side they induce tumor progression by establishing progrowth conditions in the tumor microenvironment [67,68]. The DRGs of IFN α/β signaling and cellular response to type I IFN, which were downregulated, include genes involved in tumor progression (SAMHD1 [69], PLSCR1 [70], IFITs (IFIT1, IFIT2, and IFIT3 [71]), TAPs (TAP1 and TAP2) [72], cell proliferation, apoptosis/cell survival, metastasis, angiogenesis (PSMB8 [73], PSMB9 [74], IFI6 [75], and IFI27 [76]), OAS's (OAS1, OAS2, and OAS3) [77], IFITMs (IFITM1, IFITM2, and IFITM3) [78,79], UBE2L6 [80], USP18 [81], tumorigenesis and genes with a role in cancer STAT1 [82], RSAD2 [83], IFI6 [84], and HLAs-class-I (HLA-A, HLA-B, HLA-C, HLA-F, and HLA-G) [85]). The upregulated genes (by ≥ 1.5-fold) involved in apoptosis and autophagy, cell death, and cell growth inhibition were S100A8 and S100A9 [86], MMP1 [87], MMP13 [88], AREG [89], PLIN2 [90], and AKR1C1 [91].…”

“…However, in-depth studies are required to confirm this notion. In ECs, there is a high expression of IFITM1 during sprouting and lumen formation, and these processes are disrupted by IFITM1 knockdown [79,95]. It is postulated that IFITMs regulate the transition of quiescent ECs toward an angiogenic state [79,95].…”

“…In ECs, there is a high expression of IFITM1 during sprouting and lumen formation, and these processes are disrupted by IFITM1 knockdown [79,95]. It is postulated that IFITMs regulate the transition of quiescent ECs toward an angiogenic state [79,95]. Although the role of IFITM1 in VECs is well-established, its role in LECs is unclear.…”

Proximate, nutraceutical composition and antimicrobial activities of Uvaria chamea (Udagu) seeds and oil

“…The first energy being heat which serve to maintain the body temperature. The second is free energy, which is available for work [10]. Complex macromolecule polymers of amino acids (protein) joined in peptide linkage that is very important for growth, development and maintenance that compose of 50 % of dry weight of living cells called protein that bind to other selected molecules and how their activity depends on such binding [9]; [11].…”

IFITM3 promotes glioblastoma stem cell-mediated angiogenesis via regulating JAK/STAT3/bFGF signaling pathway

“…Interferon-inducible transmembrane proteins (IFITM) comprise a family of interferon-induced molecules, consisting primarily of IFITM1, IFITM2, IFITM3 and IFITM5 [ 10 ]. During endothelial cells sprouting process in vitro, IFITM proteins were induced expeditiously and were essential for lumenized vessel formation [ 11 ]. IFITM 1–3 have been implicated in viral pathogen restriction [ 12 ].…”