Functional Impact of Human Genetic Variants of <i>COL18A1</i>/Endostatin on Pulmonary Endothelium

Goyanes, A.M.; Moldobaeva, Aigul; Marimoutou, Mery; Varela, Lidenys; Wang, Lan; Johnston, Laura; Aladdin, Meena; Peloquin, Grace; Kim, Bo S.; Damarla, Mahendra; Suresh, Karthik; Sato, Takahiro; Kolb, Todd M.; Hassoun, Paul M.; Damico, Rachel

doi:10.1165/rcmb.2019-0056oc

Cited by 23 publications

(19 citation statements)

References 48 publications

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“…The intriguing fact that PAH patients have increased endostatin levels, yet simultaneously are more likely to carry a protective missense mutation leading to lower endostatin levels, highlights the need for further in-depth investigation of the causative and functional role of endostatin. To gain functional insight, full-length and short fragments of endostatin, ES 99-111 N104 (mutated) and ES 99-111 D104 (non-mutated), were investigated [177]. The mutated peptide was less potent in inhibition of endothelial cell migration compared to non-mutated peptide and full-length endostatin, further supporting the protective phenotype of the mutated variant in PAH patients [177].…”

Section: Type XVIII Collagen and Endostatin In Phmentioning

confidence: 98%

“…While adhesion to type IV collagen triggers nuclear translocation of YAP/TAZ, adhesion to laminin α5β2γ1 retains YAP/TAZ in the cytoplasm [4]. Endostatin blocks ID-1 gene expression and decreases THBS1-transcription and production [177]. In return, TSP-1 inhibits pulmonary EC proliferation and migration via CD36/CD47, suggesting an endostatin-ID1-TSP1 axis [177].…”

Section: Figure 2 Current Knowledge On the Role Of Basement Membranementioning

confidence: 99%

“…Endostatin blocks ID-1 gene expression and decreases THBS1-transcription and production [177]. In return, TSP-1 inhibits pulmonary EC proliferation and migration via CD36/CD47, suggesting an endostatin-ID1-TSP1 axis [177]. IPAH; idiopathic pulmonary arterial hypertension; BM, basement membrane; PAs; pulmonary arteries; COL4A5, collagen type IV alpha 5 chain gene; COL14A1, collagen type XIV alpha 1 chain gene; COL18A1, collagen type XIII alpha 1 chain gene; ECs, endothelial cells; PAH, pulmonary arterial hypertension; BMPR2; bone morphogenetic protein receptor type II; β-catenin, beta catenin; COL4A1, collagen type IV alpha 1 chain gene ; COL4A2, collagen type IV alpha 2 chain gene; PAEC, pulmonary arterial endothelial cell; YAP; Yes-associated protein; TAZ, Tafazzin ; ID1, DNA-binding protein inhibitor ID-1; THBS1, thrombospondin-1 gene; TSP-1, thrombospondin-1,.…”

Section: Figure 2 Current Knowledge On the Role Of Basement Membranementioning

confidence: 99%

“…To gain functional insight, full-length and short fragments of endostatin, ES 99-111 N104 (mutated) and ES 99-111 D104 (non-mutated), were investigated [177]. The mutated peptide was less potent in inhibition of endothelial cell migration compared to non-mutated peptide and full-length endostatin, further supporting the protective phenotype of the mutated variant in PAH patients [177]. However, no effect of either of the short peptides was found on proliferation, suggesting that different regions within endostatin, or the full-length version, interfere with proliferative processes.…”

Section: Type XVIII Collagen and Endostatin In Phmentioning

confidence: 99%

“…However, no effect of either of the short peptides was found on proliferation, suggesting that different regions within endostatin, or the full-length version, interfere with proliferative processes. Full-length endostatin exerted its effects on apoptosis and migration via inhibitor of DNA binding 1/thrombospin-1 (ID-1/TSP1) axis [177] (see Figure 2).…”

Section: Type XVIII Collagen and Endostatin In Phmentioning

confidence: 99%

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Endothelial Basement Membrane Components and Their Products, Matrikines: Active Drivers of Pulmonary Hypertension?

Mutgan

Jandl

Kwapiszewska

2020

Cells

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Pulmonary arterial hypertension (PAH) is a vascular disease that is characterized by elevated pulmonary arterial pressure (PAP) due to progressive vascular remodeling. Extracellular matrix (ECM) deposition in pulmonary arteries (PA) is one of the key features of vascular remodeling. Emerging evidence indicates that the basement membrane (BM), a specialized cluster of ECM proteins underlying the endothelium, may be actively involved in the progression of vascular remodeling. The BM and its steady turnover are pivotal for maintaining appropriate vascular functions. However, the pathologically elevated turnover of BM components leads to an increased release of biologically active short fragments, which are called matrikines. Both BM components and their matrikines can interfere with pivotal biological processes, such as survival, proliferation, adhesion, and migration and thus may actively contribute to endothelial dysfunction. Therefore, in this review, we summarize the emerging role of the BM and its matrikines on the vascular endothelium and further discuss its implications on lung vascular remodeling in pulmonary hypertension.

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Section: Type XVIII Collagen and Endostatin In Phmentioning

confidence: 98%