Thrombospondins: Conserved mediators and modulators of metazoan extracellular matrix.
angiogenesis
cell adhesion
collagens
connective tissue
evolution
fibrosis
molecular phylogeny
Journal
International journal of experimental pathology
ISSN: 1365-2613
Titre abrégé: Int J Exp Pathol
Pays: England
ID NLM: 9014042
Informations de publication
Date de publication:
12 Sep 2024
12 Sep 2024
Historique:
revised:
13
08
2024
received:
30
06
2024
accepted:
18
08
2024
medline:
15
9
2024
pubmed:
15
9
2024
entrez:
13
9
2024
Statut:
aheadofprint
Résumé
This review provides a personal overview of significant scientific developments in the thrombospondin field during the course of my career. Thrombospondins are multidomain, multimeric, calcium-binding extracellular glycoproteins with context-specific roles in tissue organisation. They act at cell surfaces and within ECM to regulate cell phenotype and signalling, differentiation and assembly of collagenous ECM, along with tissue-specific roles in cartilage, angiogenesis and synaptic function. More recently, intracellular, homeostatic roles have also been identified. Resolution of structures for the major domains of mammalian thrombospondins has facilitated major advances in understanding thrombospondin biology from molecule to tissue; for example, in illuminating molecular consequences of disease-causing coding mutations in human pseudoachrondroplasia. Although principally studied in vertebrates, thrombospondins are amongst the most ancient of animal ECM proteins, with many invertebrates encoding a single thrombospondin and the thrombospondin gene family of vertebrates originating through gene duplications. Moreover, thrombospondins form one branch of a thrombospondin superfamily that debuted at the origin of metazoans. The super-family includes additional sub-groups, present only in invertebrates, that differ in N-terminal domain organisation, share the distinctive TSP C-terminal region domain architecture and, to the limited extent studied to date, apparently contribute to tissue development and organisation. Finally, major lines of translational research are discussed, related to fibrosis; TSP1, TSP2 and inhibition of angiogenesis; and the alleviation of chronic cartilage tissue pathologies in pseudoachrondroplasia.
Types de publication
Journal Article
Review
Langues
eng
Sous-ensembles de citation
IM
Informations de copyright
© 2024 Company of the International Journal of Experimental Pathology (CIJEP).
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