Disease relevance of Ift74

• We hypothesized that the growth factors modulating embryonic kidney endothelial cell survival and capillary morphogenesis may be implicated in capillary loss that occurs in immune-mediated glomerulonephritis (GN) [1].
• We hypothesized that exposure of mice to severe hypoxia would promote the expression of genes involved in capillary morphogenesis and glucose over fatty acid metabolism in active or disused soleus muscle of mice [2].
• In addition, we describe a model of capillary morphogenesis in vitro that uses microvascular endothelial cells transduced with retrovirus in culture [3].

High impact information on Ift74

• This analysis revealed that a subset of proangiogenic transcripts is preferentially translated in a Perk-dependent manner; these transcripts include VCIP, an adhesion molecule that promotes cellular adhesion, integrin binding, and capillary morphogenesis [4].
• Taken together, these results demonstrate that overexpression of TIMP-3 can inhibit angiogenesis and associated tumor growth, and that the antiangiogenic effects of TIMP-3 appear to be mediated through the inhibition of functional capillary morphogenesis [5].
• Enforced expression of tissue inhibitor of matrix metalloproteinase-3 affects functional capillary morphogenesis and inhibits tumor growth in a murine tumor model [5].
• Sonic hedgehog induces capillary morphogenesis by endothelial cells through phosphoinositide 3-kinase [6].
• Actinomycin D and cycloheximide inhibited Shh-induced capillary morphogenesis [6].

Biological context of Ift74

• These findings suggest possible roles for nuclear import and export in the regulation of cellular TTP, CMG1, and TIS11D activity [7].
• In the diabetic this burst of DNA replication was absent and no capillary morphogenesis was seen at two, four, and eight hours [8].
• The two other known mammalian members of the TTP family, CMG1 and TIS11D, also contain ARE-binding CCCH tandem zinc finger domains and can also destabilize ARE-containing mRNAs [7].
• To understand the mechanisms underlying these cellular responses in angiogenesis, we studied the Rho family protein-driven pathways in FGF-2-induced chemotaxis and capillary morphogenesis of murine brain capillary endothelial cell line, IBE cells [9].

Anatomical context of Ift74

• The lack of DNA replication, capillary morphogenesis, fibroblast RER proliferation, and decreased collagen synthesis in the diabetic mouse can be considered interrelated and significant factors in the diabetic's impaired response to cellular injury [8].
• To investigate the effects of primary sequence on the subcellular localization of these proteins, we constructed green fluorescent protein fusions with TTP, CMG1, and TIS11D; these were predominantly cytoplasmic when expressed in 293 or HeLa cells [7].
• KDPAK1 cells formed stress fibers and showed capillary morphogenesis in response to FGF-2 [9].
• Increase in focal adhesions was closely associated with capillary morphogenesis [9].
• CMG-1 transcripts were predominantly produced in spermatogonia and spermatocytes in mouse testis [10].

Associations of Ift74 with chemical compounds

• Shh-induced capillary morphogenesis was also blocked by LY294002, a phosphoinositide 3-kinase (PI3-kinase) inhibitor [6].
• On Matrigel, DNRho and Y27632 induced FGF-2-independent capillary morphogenesis despite loss of stress fiber formation [9].

Other interactions of Ift74

• Studies of capillary morphogenesis and angiogenesis in vitro have suggested a role for E-selectin (CD62E) in the process of differentiation into tube-like structures [11].
• When CMG-1 expression was attenuated in a mouse spermatocyte-derived cell line, GC-2spd(ts), by a target-specific short interfering RNA, the morphology of the cells was changed and the expression of cyclin D2 was abrogated [10].

References