Type V collagen regulates the assembly of collagen fibrils in cultures of bovine vascular smooth muscle cells.
Vascular smooth muscle cells (SMCs), the major cellular constituent of the medial layer of an artery, synthesize the majority of connective tissue proteins, including fibrillar collagen types I, III, and V/XI. Proper collagen synthesis and deposition, which are important for the integrity of the arterial wall, require the antioxidant vitamin C. Vitamin C serves as cofactor for the enzymes prolyl and lysyl hydroxylase, which are responsible for the proper hydroxylation of collagen. Here, the role of type V collagen in the assembly of collagen fibrils in the extracellular matrix (ECM) of cultured vascular SMCs was investigated. Treatment of SMCs with vitamin C resulted in a dramatic induction in the levels of the cell-layer associated pepsin-resistant type V collagen, whereas only a minor induction in the levels of types I and III collagen was detected. Of note, the deposition of type V collagen was accompanied by the formation of striated collagen fibrils in the ECM. Immunohistochemistry demonstrated that type V collagen, but not type I collagen, became masked as collagen fibrils matured. Furthermore, the relative ratio of type V to type I collagen decreased as the ECM matured as a function of days in culture, and this decrease was accompanied by an increase in the diameter of collagen fibrils. Together these results suggest that the masking of type V collagen is caused by its internalization on continuous deposition of type I collagen on the exterior of the fibril. Furthermore, they suggest that type V collagen acts as framework for the initial assembly of collagen molecules into heterotypic fibrils, regulating the diameter and architecture of these fibrils.
Kypreos
K E
KE
Department of Biochemistry, Boston University School of Medicine, Boston, Massachusetts 02118, USA.
Birk
D
D
Trinkaus-Randall
V
V
Hartmann
D J
DJ
Sonenshein
G E
GE
D000818:Animals; D002417:Cattle; D002478:Cells, Cultured; D003094:Collagen / Q000378:metabolism* / Q000648:ultrastructure; D005109:Extracellular Matrix / Q000378:metabolism / Q000648:ultrastructure; D007150:Immunohistochemistry; D008854:Microscopy, Electron / Q000379:methods; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000378:metabolism* / Q000648:ultrastructure
D003094:Collagen