COLLAGEN XVIII REGULATES BASEMENT MEMBRANE INTEGRITY, ACTA UNIVERSITATIS OULUENSIS D Medica 1095
|Kustantaja:||Oulun yliopisto|| |
|Laitos:||Lääketieteellinen tiedekunta|| |
|Sijainti:||Print Tietotalo|| |
|Tekijät:||KINNUNEN AINO || |
Collagen XVIII is a multidomain basement membrane proteoglycan with three tissue-specificisoforms. Endostatin, the C-terminal part of collagen XVIII, has antiangiogenic properties, whilethe frizzled-like domain of the longest isoform is suggested to be capable of inhibiting the Wnt/â-catenin signaling network. This study utilized several genetically modified mouse lines andelectron microscopy to achieve new information on the biological role of collagen XVIII, itsdifferent isoforms, and the frizzled domain.
Lack of collagen XVIII was found to affect the integrity of basement membranes of varioustissues, leading to an abnormally loosened network structure. In the choroid plexus, the change inthe basement membrane ultrastructure caused alterations in the production of the cerebrospinalfluid and predisposed to the development of hydrocephalus. In the kidney, broadening of theproximal tubular basement membrane was shown to be due specifically to the lack of the shortisoform, while the lack of the two longer isoforms led to podocyte foot process effacement.Moreover, lack of collagen XVIII was found to cause softening of the kidney glomeruli and thelevels of serum creatinine were elevated in the mutant animals, indicating altered kidney function.
The hair follicle cycle was used as a model to study the possible role of the frizzled domain ofcollagen XVIII in the Wnt/â-catenin signaling cascade. The longer collagen XVIII isoforms wereshown to be expressed in the basement membrane facing the dermal papilla and in the hair folliclebulge, containing the follicular stem cells. Lack of the long isoforms led to abnormalities in theprogression of the first hair cycle, and the phenotype could be rescued via transgenic delivery ofthe frizzled domain of the longest isoform, suggesting its involvement in the regulation of the Wnt/â-catenin signaling network during the cyclic growth of the hair.