Type IV collagens are the most abundant proteins in basement membranes. Distinct genes encode each of six isoforms, alpha1(IV) through alpha6(IV), which assemble into one of three characteristic heterotrimers. Disease-causing mutations in each of the six genes are identified in humans or mice and frequently include diverse ocular pathogenesis that encompass common congenital and progressive bli...

Tumor cell motility and the passage of tumor cells through various tissue matrices, including basement membrane, are important components of the metastatic process. Proteolytic enzymes, including a type IV collagen-specific collagenase, have been demonstrated to play a significant role in extracellular matrix and basement membrane degradation. In addition, exogenous collagenase has been shown t...

Type IV collagen incubated at elevated temperatures in physiologic buffers self-associates (a) via its carboxy-terminal (NC1) domain, (b) via its amino-terminal (7S) domain, and (c) laterally; and it forms a network. When examined with the technique of rotary shadowing, isolated domain NC1 was found to bind along the length of type IV collagen to four distinct sites located at intervals of appr...

Introduction: During nephrogenesis, transition of mesenchyme to the epithelium of tubules and glomeruli occurs via the interaction of ureteral bud and metanephric mesenchyme. The distribution pattern of collagen type IV suggests that a regulated balance of activities is required to facilitate migration of the ureteral bud branches into the mesenchyme and to control early extracellular matrix ch...

Primary cultures of rat mammary epithelial cells proliferate and synthesize basement membrane collagen (type IV collagen) in a serum-free medium supplemented with epidermal growth factor (EGF), hydrocortisone or dexamethasone, insulin, transferrin, and Pedersen fetuin. The growth response of the cells to EGF and glucocorticoids but not to insulin or transferrin varies depending on the substratu...

Tumor cells traverse basement membranes (BM) during the stages of the metastatic process. Penetration of the BM may involve proteolysis by enzymes directly or indirectly associated with tumor cells. This study evaluated the role of the serine proteases urokinase (plasminogen activator), plasmin, and another regulatory protease, alpha-thrombin, in the degradation of the BM. Homogeneously pure en...

Type IV collagen has the ability to self-assemble by amino end, carboxyl end, and lateral associations to complex network-like structures which can be visualized by rotary shadowing. The main noncollagenous NC1 domain which is located at the carboxyl end of type IV collagen molecules binds to itself to form dimers and also binds along the length of type IV collagen. The latter binding initiates...

Diabetic nephropathy (DN) affects both glomerular cells and the extracellular matrix (ECM), yet the pathogenic mechanisms involving cell-matrix interactions are poorly understood. Glycation alters integrin-dependent cell-ECM interactions, and perturbation of these interactions results in severe renal pathology in diabetic animals. Here, we investigated how chemical modifications of the ECM by h...

Platelet activation and aggregation by fibrillar collagens are based on substrate primary, secondary, tertiary, and quaternary structure. Although several peptides incorporating sequences from the triple-helical domains of types I and III collagen inhibit collagen-mediated platelet aggregation, none independently promote platelet activation and aggregation. It is believed that the absence of th...

BACKGROUND The plasma concentration of 5-hydroxytryptamine (5-HT) in diabetic patients is higher than that in normal subjects. Since recent reports have demonstrated the presence of 5-HT2A receptor in glomerular mesangial cells, it is possible that 5-HT may be involved in the development of diabetic nephropathy through the 5-HT2A receptor in mesangial cells. Because expansion of the glomerular ...