TGFβ signaling regulates Col15a1 expression in fenestrated endothelial cells of the rat pituitary

Abstract Fenestrated capillaries in the anterior lobe (AL) of the pituitary gland are specialized capillary networks that facilitate efficient hormone exchange and are surrounded by extracellular matrix-rich basement membranes (BMs). Although several collagens have been implicated in the structural regulation of capillaries in the pituitary, the contribution of collagen XV remains unknown. In the present study, we investigated the expression, localization, and regulation of COL15A1, the α1 chain of collagen XV, in the rat pituitary. Real-time quantitative PCR and in situ hybridization revealed that Col15a1 is highly expressed in PLVAP (plasmalemma vesicle–associated protein), a marker of fenestrated endothelial cells, -positive fenestrated endothelial cells in the AL. Immunohistochemistry demonstrated that COL15A1 is localized to BMs surrounding PLVAP-positive fenestrated capillaries in the AL, the median eminence, and the choroid plexus, but not in those surrounding continuous capillaries in the cerebrum. These findings identify collagen XV as a novel BM component associated with fenestrated capillaries. Because transforming growth factor-β (TGFβ) is a key regulator of collagen expression, we examined its role in Col15a1 regulation. Tgfbr2 was expressed in fenestrated endothelial cells in the AL, and TGFβ1 stimulation induced nuclear translocation of SMAD2 in cultured endothelial cells isolated from the rat AL. TGFβ1 significantly increased Col15a1 expression, which was suppressed by the TGFβ receptor I inhibitor SB431542. Together, these results demonstrate that TGFβ signaling regulates Col15a1 expression in fenestrated endothelial cells and suggest that collagen XV contributes to the structural and functional specialization of fenestrated capillaries in the pituitary.