Collagen XVIII Regulates Basement Membrane Integrity: Specific Effects of Its Isoforms on the Choroid Plexus, Kidney, and Hair Follicle

This study investigated the role of collagen XVIII and its isoforms in maintaining basement membrane integrity across various tissues, using genetically modified mouse models and electron microscopy. It was found that the absence of collagen XVIII led to compromised basement membrane structures, affecting the choroid plexus, kidney, and hair follicles. In the choroid plexus, this resulted in altered cerebrospinal fluid production and increased risk of hydrocephalus. In the kidney, the lack of the short isoform caused broadening of the proximal tubular basement membrane, while the absence of longer isoforms led to podocyte foot process effacement and impaired kidney function, as indicated by elevated serum creatinine levels. The study also explored the involvement of the frizzled domain of collagen XVIII in the Wnt/β-catenin signaling pathway during hair follicle cycling. The absence of long isoforms disrupted the first hair cycle, but this was corrected by transgenic delivery of the frizzled domain, highlighting its regulatory role in hair growth.