Expression and Localization of Tenomodulin, a Transmembrane Type Chondromodulin-I-Related Angiogenesis Inhibitor, in Mouse Eyes

Abstract

These results indicate a potential role for TeM in prevention of vascular invasion in the mouse eye and the possibility of both TeM and ChM-I as candidates for use in gene therapy approaches to treatment of ocular 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 …”

A Prospectus of Tenomodulin

“…4 It has been shown that the TNMD protein can have different forms. 3,5,7,12 For example, TNMD has been detected as N-glycosylated and non-Nglycosylated form with molecular mass of 45 and 40 kDa, respectively. 3 The same forms are found in pigs, namely in pigs' chordae tendineae cordis (CTC) and pigs' eye.…”

“…12 These forms have been also found in mice. 5,7 More specifi cally, a 16-kDa secreted form cleaved in a tissue-specifi c manner has been detected in the porcine CTC, but not in the eye. N-terminal part of the protein has been presented in the CTC, as well.…”

“…4 The name originates from tenocytes, the tendon cells, as tenomodulin is predominantly expressed in tendons. 2,4,5 The offi cial abbreviation of the human tenomodulin gene is TNMD.…”

“…A lot of studies confi rmed its important role in the tendon differentiation 4,6 and in the inhibition of angiogenesis 5,7 . Tenomodulin regulates various biological processes, but most of its functional mechanisms are still unknown.…”