Prof. Taina Pihlajaniemi and Adj. Prof. Ritva Heljasvaara

Short CV

Conserved Collagens in Cell–Matrix Homeostasis

Besides conferring shape and stability to tissues, the extracellular matrix (ECM) plays a crucial role in controlling cell differentiation and function, and it is associated with a wide spectrum of common diseases including arthritis, atherosclerosis, cancer, fibrosis, skeletal deformity and poor wound healing. The collagen family of proteins plays a dominant role in maintaining the integrity of tissues. Twenty-nine types of collagen have been found in vertebrates, and we address the physiological and pathological significance of two evolutionarily conserved subgroups of collagens, the ubiquitously occurring basement membrane (BM)-associated collagens XV and XVIII, also called the multiplexin subgroup of collagens, and the structurally homologous transmembrane collagens XIII, XXIII and XXV. These collagens perform not only structural functions but also have important regulatory roles in the pericellular environment in supporting cell growth and differentiation.

Collagen XIII has been shown to occur both as membrane-bound and shed protein. As a result of its location at many cell–matrix junctions and in focal adhesions in cultured cells it conceivably has a function in cell adhesive processes. Human disorders arising from mutations in this collagen have not been identified, but our work with genetically modified mice suggests functional roles for collagen XIII at least in bone, peripheral nerves, muscle and placenta. Collagens XV and XVIII are multidomain proteins found in association with most BMs. Although single and double knockout mice as regards collagens XV and XVIII are viable and fertile, the lack of these related collagens affects the integrity of several organs and tissues such as eyes, brain ventricles, skeletal muscle, heart and blood vessels. Mutations in collagen XVIII lead to the rare inherited Knobloch syndrome, characterised by myopia and other eye abnormalities and in some cases by occipital encephalocele. Collagen XVIII has also aroused much interest on account of its C-terminal endostatin domain, which has been shown to inhibit angiogenesis and tumour formation. With respect to collagen XV, we have shown that its lack in mice leads to defects in skeletal muscle, heart and peripheral nerves. Both the transmembrane and endostatin collagens are associated with malignant processes. The project is part of the Finnish Centre of Excellence Programme funded by the Academy of Finland (Centre of Excellence Grant 2012 - 2017).

Project details

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Last updated: 8.6.2020