Fig. 2.

Endocytic collagen receptors uPARAP/Endo180 and MR regulate collagens in disease. a uPARAP/Endo180 deficiency results in increased collagen accumulations after systemic CCl₄ treatment in a mouse model of liver fibrosis. In this study, collagen levels in tissue sections from control livers (isolated from vehicle-injected mice) or fibrotic livers from wild-type mice or uPARAP/Endo180-deficient littermates injected with CCl₄ in the peritoneum twice a week for 6 weeks were determined using Picrosirius Red staining and computer-assisted image analysis. Reproduced with permission from Wiley [17]. b uPARAP/Endo180 deficiency results in increased accumulation of collagen in a genetic model of mouse mammary tumors. Collagen levels were determined using immunohistochemical staining for collagen type I on tissue sections from mammary tumors isolated from female mice carrying the MMTV–PyMT transgene. Tumors were isolated from uPARAP-expressing mice (representative image in top left panel) or uPARAP/Endo180-deficient littermates (representative image in bottom left panel). Scale bar: 500 µm. The level of endogenous collagen inside tumors was determined using histomorphometric analysis (right panel). Reproduced with permission from Rockefeller University Press [16]. c MR drives the cellular uptake of collagens by TAMs and MR-deficiency results in increased collagen accumulation in a transplanted LLC tumor model. Fluorescently-labelled collagen was injected into syngeneic LLC tumors implanted in the subcutaneous space of C57BL/6 mice and the cellular uptake of collagen was visualized using confocal imaging of intact tumors isolated from wt mice (MRC1 + / + , upper left panel) and MR-deficient littermates (MRC1 −/−, upper right panel). The number of TAMs (F4/80 + CD11b +) with a high level of collagen uptake was quantified using flow cytometry-based analysis of single-cell suspensions generated by mechanical and enzymatical digestion of tumors (lower left panel). Intratumoral collagen levels in tumors from wt mice and MR-deficient littermates were determined using Picrosirius Red stainings of tumor tissue sections (lower center panels) and computer-assisted image analysis (lower right panel). Reproduced with permission from CellPress [10]