COLLAGEN XV AS A MATRIX ORGANIZER, ACTA UNIVERSITATIS OULUENSIS D Medica 1083
|Kustantaja:||Oulun yliopisto|| |
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|Tekijät:||RASI KAROLINA|| |
Collagen XV is a proteoglycan localized in the outermost layer of the basement membrane (BM)and in the fibrillar matrix. Although it is widely distributed in many tissues, its amount is generallylow. It is characterized by a highly interrupted collagenous domain flanked by large globulardomains and attached glycosaminoglycan chains, thus also being identified as a chondroitinsulphate proteoglycan. The C-terminal end of collagen XV, termed restin, has proved to haveantiangiogenic effects. In view of its location in the outermost layer of the lamina densa and inassociation with interstitial collagen fibrils near BMs, it has been suggested that collagen XV mayform a bridge between the fibrillar collagen matrix and the BMs. In vivo studies of mice lackingcollagen XV have demonstrated that collagen XV is needed as a structural component to stabilizethe skeletal muscle cells and capillaries.
The role of collagen XV in the extracellular matrix (ECM) was studied using a mouse modellacking the gene of interest (Col15a1-/-). The matrix of peripheral nerves, skeletal muscle, heartand the uterus during pregnancy was analysed at several time points, and peripheral nervedevelopment was evaluated in a mouse model lacking collagen XV and the laminin á4 chainsimultaneously as well as in Col15a1-/- mice. The function of collagen XV in the heart wasanalysed in young, adult and old mice separately.
The results indicate that collagen XV is needed for organizing collagen fibrils into properbundles in the cardiac ECM. In the developing nerve it regulates collagen fibril size and theorganization of the fibrils within the collagen bundle. In mature nerves and skeletal muscles itstructures the BM–fibrillar matrix interphase, and in the uterus of pregnant mice it participates infibrillar collagen remodelling, affecting the lateral fusion of collagens into thick fibrils. Evendelicate changes in the matrix can lead to an alteration in the functioning of certain organs.Abnormal C-fibrils, polyaxonal myelination and decreased sensory conduction velocity wereobserved in the Col15a1-/- peripheral nerves, and a simultaneous lack of collagen XV and thelaminin á4 chain resulted in more severe and permanent impairment of the segregation andmyelination of the nerve axons. A complex cardiac phenotype was observed in the Col15a1-/-mice, predisposing them to cardiomyopathy.