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- W2239983587 abstract "Collagen XVIII is an evolutionarily conserved, ubiquitously-expressed basement membrane (BM) proteoglycan produced in three isoforms, the individual roles of which are largely unknown. The physiological in vivo roles of these collagen XVIII isoforms are studied here using novel genetically modified mouse strains deficient in either the short or the medium/long isoforms of the molecule. In addition, the effects of keratin-14-driven overexpression of the thrombospondin-1 (Tsp-1) –like domain, which is common to all three collagen XVIII isoforms, are studied. The findings underline the importance of the short collagen XVIII isoform in the eye, as its absence was sufficient to cause the aberrant vascularisation of the retina previously reported in mice lacking all isoforms of collagen XVIII. In addition, an excess of the collagen XVIII Tsp-1 domain led to serious eye abnormalities, possibly by interfering with the functions of the fulllength collagen XVIII produced in mice. Collagen XVIII was also shown to contribute to adipogenesis in an isoform-specific manner, in that a lack of the medium/long isoforms of collagen XVIII led to impaired adipocyte maturation and the subsequent reduction in the adipocyte number induced liver steatosis and hypertriglyceridaemia. Hence this work establishes a new extracellular matrix (ECM)-directed mechanism contributing to control over the multistep adipogenesis programme and points to the functional consequences of its impairment for ectopic fat deposition. The enzymatic remodelling of ECM components results in molecules with novel biological activities. Arresten is a collagen IV(α1)-derived fragment with anti-angiogenic properties which was originally described as not having any direct anti-tumour effects on cancer cells themselves. The present data revealed novel inhibitory roles for arresten in oral squamous carcinoma cell proliferation, survival, motility and invasion. Since arresten is a potent inhibitor of angiogenesis, the data generated here further underline the possibility for using it as a therapeutic agent in cases of cancer." @default.
- W2239983587 created "2016-06-24" @default.
- W2239983587 creator A5067909623 @default.
- W2239983587 date "2013-01-01" @default.
- W2239983587 modified "2023-09-23" @default.
- W2239983587 title "Novel roles for basement membrane collagens : isoform-specific functions of collagen XVIII in adipogenesis, fat deposition and eye development, and effects of the collagen IV-derived matricryptin arresten on oral carcinoma growth and invasion" @default.
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