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The distribution of the collagen chains from αα1(IV) to αα6(IV) could serve as a basis for the characterization of type IV collagen. In this study, immunohistochemistry of the ocular anterior segment of adult mice was performed using specific monoclonal antibodies against each chain in the series from αα1(IV) to αα6(IV). The results show that the components of type IV collagen in vascular basement membranes are αα1(IV) and αα2(IV) with or without αα5(IV) and αα6(IV) chains and those in epithelium and muscle basement membranes are αα1(IV), αα2(IV), αα5(IV), and αα6(IV) chains. In corneal endothelium, pigmented epithelium of iris and ciliary body, and trabecular meshwork, αα3(IV) and αα4(IV) chains are also expressed in addition to αα1(IV), αα2(IV), αα5(IV), and αα6(IV) chains. Moreover, we investigated the change in molecular composition in ciliary body during postnatal development. αα3(IV) and αα4(IV) chains were also expressed in addition to αα1(IV), αα2(IV), αα5(IV), and αα6(IV) chains in ciliary pigmented epithelium basement membrane from 7 days after birth. This result suggests that the basement membranes gradually change their biochemical features owing to temporal regulation. Taken together, these findings suggest that the different distribution and the developmental expression of αα1(IV) to αα6(IV) chains are associated with the tissue-specific function of type IV collagen in basement membranes. [ABSTRACT FROM AUTHOR]

Following brain injury, thrombospondin-1 (TSP-1) is involved in angiogenesis and synaptic recovery. In this study, we used a cold injury-model and found that TSP-1 mRNA was markedly upregulated after brain injury. Immunohistochemistry showed that TSP-1 was upregulated in both the core of the lesion and in the perilesional area of injured brain tissue. Numerous astrocytes immunopositive for glial fibrillary acidic protein (GFAP) were found in the perilesional area, and TSP-1 was also expressed in almost all astrocytes surrounding blood vessels at 4 days after injury. Next, we examined the influence of vascular basement membrane components on TSP-1 expression. When astrocytes were cultured on type IV collagen, TSP-1 was significantly upregulated compared with the expression when cells were grown on laminin, fibronectin, or poly-L-lysine. This increase occurred exclusively when astrocytes were grown on the native form of type IV collagen but not on the heat-denatured form or the non-collagenous 1 domain. Further, integrin alpha1 and beta1 mRNAs were upregulated concomitantly with GFAP mRNA, and integrin alpha1 protein was localized to the endfeet of astrocytes that surrounded blood vessels in the injured brain. Using function-blocking antibodies, we found that the effect of type IV collagen was attributed to integrin alpha1beta1 in primary astrocytes. Collectively, our results suggest that vascular basement membrane components substantially impact gene expression in astrocytes during brain tissue repair.