A novel brain-specific p53-target gene, BAI1, containing thrombospondin type 1 repeats inhibits experimental angiogenesis

Circulating IGF-1 deficiency exacerbates hypertension-induced microvascular rarefaction in the mouse hippocampus and retrosplenial cortex: implications for cerebromicrovascular and brain aging

“…Figure 6 shows the effects of IGF-1 deficiency and hypertension on the hippocampal expression of the angiogenesis inhibitors Serpinf1 (PEDF), f i b u l i n -5 ( F b l n 5 ) ( S u l l i v a n e t a l . 2 0 0 7 ) , thromhospondin-1 (Thbs1) (Lawler 2002), Thbs2 (Volpert et al 1995), the potent anti-angiogenic chemokine platelet factor 4 (Pf4) (Bikfalvi 2004); vasohibin-1 (Vash1), which is a newly recognized (Takano et al 2014), Adamts1 ("a disintegrin and metalloproteinase with thrombospondin motifs 1"), which inhibits angiogenesis (Lee et al 2006) by suppressing endothelial cell proliferation; Col18a1, whose expression level impacts endostatin signaling and endothelial angiogenic capacity (Li and Olsen 2004) (endostatin, a potent inhibitor of angiogenesis, is a 20-kDa C-terminal fragment derived from type XVIII collagen); semaphorin-3F (Sema3f) (Ungvari et al 2011b;Frisbee et al 2007); tenomodulin (Tnmd) (Oshima et al 2003); brainspecific angiogenesis inhibitor 1 (Bai1; also known as adhesion G protein-coupled receptor B1 [ADGRB1]) (Nishimori et al 1997); chromogranin A (Chga), which encodes the precursor to several angiogenesis inhibitor peptides including vasostatin-1 and vasostatin-2 (Helle and Corti 2015) and maspin ("mammary serine protease inhibitor"; encoded by the Serpinb5 gene (Qin and Zhang 2010). Figure 7 shows the expression of Tnfa, whose overproduction has been causally linked to microvascular rarefaction (Frisbee et al 2014); Tgfb1, which regulates multiple aspects of the angiogenic process and contributes to hypertension-induced microvascular rarefaction in the heart (Koitabashi et al 2011); Tgfa; angiogenin (Ang, also known as ribonuclease 5), which is a potent stimulator of angiogenesis and an inhibitor of endothelial apoptosis; Edil3 (EGF-like repeats and discoidin Ilike domains 3), which encodes a glycoprotein secreted by endothelial cells that regulates apoptosis, cell migration (Zhong et al 2003) and induces cerebral angiogenesis in mice (Fan et al 2008); midkine (Mdk, also known as neurite growth-promoting factor 2 or NEGF2), which is a pleiotropic growth factor regulating cell proliferation, cell migration and promoting angiogenesis (Mashour et al 2001 [HB-GAM]), which is a pro-angiogenic growth factor that is structurally related to midkine and whose expression in the adult brain is induced by ischemia; Tymp (thymidine phosphorylase, also known as platelet-derived endothelial cell growth factor [ECGF1], which stimulates endothelial cell proliferation and induces angiogenesis in the brain …”

Antiangiogenic activity of BAI1 in vivo: implications for gene therapy of human glioblastomas

“…BAI1 mRNA was detected by hybridization of membranes with 32 P-labeled BAI1 cDNA as previously reported. 8 To check the quality of loaded mRNA, blots were also hybridized with a 32 P-labeled b-actin cDNA. The cDNA probes were labeled with [ 32 P]dCTP (Amersham life Sciences) by the random-primer method to a specific activity of 42 Â 10 9 dpm/mg.…”

“…They did not examine the role of p53 in regulating BAI1 mRNA expression in glioma cells, however. 8 Interestingly, a recombinant protein containing the TSP-type 1 repeats of BAI1 inhibited the in vivo neovascularization induced by bFGF on rat corneas. Taken together, these results suggest that BAI1 might play a significant role in the inhibition of angiogenesis downstream of p53.…”

Activation and activities of the p53 tumour suppressor protein

“…Activated p53 leads to cell cycle arrest and apoptosis, and can play a role in the induction of differentiation and cellular senescence (Almog and Rotter, 1997; Lundberg et al, 2000). Wild-type p53 has been shown to inhibit angiogenesis in tumours, by activating or repressing genes that regulate new blood vessel formation (Dameron et al, 1994;Nishimori et al, 1997;Bouvet et al, 1998). p53 can also play a direct role in the repair of DNA damage, both through nucleotide excision repair and base excision repair (Ford and Hanawalt, 1995;Wani et al, 1999;Offer et al, 2001;Zhou et al, 2001).…”