Disease relevance of Flt1

• Alterations in the immunohistochemical distribution patterns of vascular endothelial growth factor receptors Flk1 and Flt1 in bleomycin-induced rat lung fibrosis [1].
• VEGF and VEGF receptor expression after experimental brain contusion in rat [2].
• VEGFR-1 mRNA was present beneath the inner limiting membrane and in the ganglion cell layer, inner nuclear layer, outer plexiform layer, and outer limiting membrane of the retina; it was also detected in blood vessels, the ciliary body, and the cornea [3].
• In addition, VEGF mRNA and VEGFR mRNAs were found to be overexpressed in most adenocarcinomas and squamous cell carcinomas as well as in one to three of the five adenomas tested [4].
• Chronic treatment of rats with the VEGF receptor blocker SU5416 led to enlargement of the air spaces, indicative of emphysema [5].

High impact information on Flt1

• In contrast, overexpression of placental growth factor, which signals through Flt1 but not kinase insert domain protein receptors (KDRs), had negative effects on neurogenesis and inhibited learning, although it similarly increased endothelial cell proliferation [6].
• In addition, however, the demonstration of functional VEGF receptor expression by Schwann cells indicates a direct effect of VEGF on neural integrity as well [7].
• Here we report the unexpected finding that treatment with truncated soluble Flt-1 receptors, which inhibit vascular endothelial growth factor (VEGF) bioactivity, resulted in virtually complete suppression of CL angiogenesis in a rat model of hormonally induced ovulation [8].
• The VEGF receptor inhibitor SU5416 induced alveolar septal cell apoptosis but did not inhibit lung cell proliferation [5].
• We conclude that VEGF in the isolated perfused lung acts as an early gene in response to hypoxia and that lung VEGF and VEGF receptor mRNA levels are influenced by hypoxia and NO-dependent mechanisms [9].

Chemical compound and disease context of Flt1

• Transactivation of the VEGFR-MAPK cascade by DALN involved CB1 cannabinoid receptors coupled to Gi/Go GTP-binding proteins as it was blocked by SR141716A and by pertussis toxin (PTX) [10].

Biological context of Flt1

• In conclusion, we have demonstrated that TBI leads to an upregulation of VEGF, Flt-1, and Flk-1 mRNA and protein in and around the lesion [2].
• These findings suggest that: (1) exercise alters Flt-1 and Flk-1 gene expression; and (2) NO is important in the regulation of the Flt-1 gene response to exercise [11].
• These findings suggest that VEGF receptor signaling is required for maintenance of the alveolar structures and, further, that alveolar septal cell apoptosis contributes to the pathogenesis of emphysema [5].
• A number of clinical and experimental studies suggest that tumor-induced lymphangiogenesis driven by vascular endothelial growth factor (VEGF)-C- and/or VEGF-D-induced activation of VEGF receptor (VEGFR)-3 may promote metastasis to regional lymph nodes [12].
• This transactivation was blocked by the selective inhibitor of VEGF receptor tyrosine kinase activity but not by inhibitors of epidermal growth factor receptor or protein kinase C activity [13].

Anatomical context of Flt1

• In control lungs, Flt1 immunoreactivity was present in ciliated bronchial epithelium and type 2 pneumocytes, Flk1 in Clara cells, and VEGF in Clara cells and type 2 pneumocytes [1].
• A new communication system between hepatocytes and sinusoidal endothelial cells in liver through vascular endothelial growth factor and Flt tyrosine kinase receptor family (Flt-1 and KDR/Flk-1) [14].
• It was also noted that Flt-1/Flk-1 and VEGF-positive vessels often were negative for SMI-71, a marker for vessels in areas with blood-brain barrier (BBB) [2].
• Attenuation of the exercise-induced increase in skeletal muscle Flt-1 mRNA by nitric oxide synthase inhibition [11].
• On the other hand, VEGFR-1 was demonstrated in smooth muscle fibers, particularly in those that surround vessel endothelium, the endothelial expression being very low in control and orchidectomized rats [15].

Associations of Flt1 with chemical compounds

• To investigate the role of vascular endothelial growth factor (VEGF) in fibrogenesis, the distribution patterns of the VEGF receptors Flt1 and Flk1 were studied by immunohistochemistry, double immunofluorescence, and immunoelectron microscopy in normal (n=2) and bleomycin-treated (n=21) adult rats [1].
• Eight groups [Condition: Rest or Exercise; Drug: Saline, 30 mg kg(-1)N(omega)-nitro-L-arginine methyl ester (L-NAME), 300 mg kg(-1) L-NAME or 300 mg kg(-1) D-NAME] were used to determine the effect of NOS inhibition on the Flt-1 mRNA response to exercise [11].
• Positive immunolabelling with Factor VIII, Flt1 and CD 34 antibodies suggests that this new RCP cell line originated from endothelial cells of rat choroid plexus [16].
• Flt-1, Flk-1, and ACE-containing cells were detected in 3% O2-treated explants, whereas 20% O2 explants were virtually negative [17].
• Expression of vascular endothelial growth factor and its receptors Flt-1 and KDR/Flk-1 in chronic cyclosporine nephrotoxicity [18].

Regulatory relationships of Flt1

• RESULTS: VEGFR-2 mRNA and protein expression were up-regulated without an increase in VEGF or VEGFR-1 expression [19].
• VEGF and VEGF receptor expression are upregulated by hypoxia in vivo and the role of VEGF in hypoxia-induced angiogenesis has been extensively studied in a variety of disease entities [20].
• In this study AngII upregulated VEGF and Flt-1 expression in myoFb, but not KDR; this was mediated predominantly by AT1-receptor [21].

Other interactions of Flt1

• RT-PCR and Western blot analyses showed an increased expression of either mRNA or VEGF-A protein after MCP-1 activation (10-100 pg/ml), whereas no fms-like tyrosine kinase (Flt)-1 receptor upregulation was observed [22].
• In contrast, platelet-derived growth factor-BB and basic fibroblast growth factor had no effect on VEGF expression, but strongly induced FLT-1 mRNA levels [23].
• VEGF-C and VEGF-D are lymphangiogenic factors that bind to and activate VEGFR-3, a fms-like tyrosine kinase receptor whose expression is limited almost exclusively to lymphatic endothelium in the adult [24].
• METHODS AND RESULTS: Exposure to hypoxia induced a potentiation of cultured cell proliferation in response to either the agonist for the VEGF receptor 1 (flt-1) placental growth factor (PlGF-1) or to VEGF-A [25].
• Aldosterone reduced the mRNA levels of vascular endothelial growth factor (VEGF) receptor (VEGFR) 2 without having any effect on the production of VEGF or mRNA levels of VEGF and hepatocyte growth factor in the progenitor cells [26].

Analytical, diagnostic and therapeutic context of Flt1

• Lungs were studied at 5, 24, 28, 35, and 42 days after treatment (p.t.). Flt1, Flk1, and VEGF immunoreactivity localised predominantly to the pulmonary epithelium [1].
• Expression of VEGF and the VEGF receptors VEGFR1 (Flt-1) and VEGFR2 (Flk-1) were studied by in situ hybridization and immunohistochemistry [2].
• In female Wistar rats, the VEGF receptor messenger RNA (mRNA) response to a single acute exercise bout was examined using semi-quantitative Northern blot from the left gastrocnemius muscles at rest and post-exercise at 0, 1, 2, 4, 8, 16, 24 and 48 h [11].
• Aging and orchidectomy modulate expression of VEGF receptors (Flt-1 and Flk-1) on corpus cavernosum of the rat [15].
• Reduced-cycle, specific-primer, reverse-transcriptase polymerase chain reaction was performed to determine the expression of VEGF and its receptors, VEGFR-1 and VEGFR-2 [27].

References