The major constituent of basement membrane is type (IV) collagen. It consists of two genetically distinct polypeptide chains, pro alpha1 (IV) and pro alpha2 (IV) with apparent molecular weights of 180 and 170 kDa respectively. The turnover of basement membranes is an active area of research with significant implications for the maintenance of normal structure and function. The lens capsule plays an important role in the pathogenesis of anterior subcapsular cataracts, for instance Lowe's syndrome and Down's syndrome. There is very little information available regarding specific biochemical defects that underlie these diseases. Consequently, study of the synthesis and regulation of type (IV) collagen should yield relevant information. Recently, we have demonstrated that epithelial cells cultured from bovine anterior lens capsule explants synthesize and secrete procollagen type (IV) polypeptide chains alpha1 (IV) and alpha2 (IV). Also, poly (A+) mRNA isolated and translated in a cell- free system synthesizes type IV collagen chains. We propose to investigate the basic mechanisms that regulate extracellular matrix production in normal epithelial cells. Our approach will be to investigate the factors and the mechanisms which control the expression of specific extracellular matrix genes. The focus of the present studies is on the type IV collagen of the extracellular matrix. The current techniques of recombinant DNA will be used to study gene expression in cultured epithelial cells. Our approach will be to develop specific DNA probes and using these probes we aim to test the hypothesis that environmental factors like retinoic acid, dexamethasone, glucose, galactose and insulin regulate the expression of type IV collagen in the model system. It is reasonable to believe that under the influence of these modulators, morphological abnormality of epithelial cells may be preceded by biochemical and molecular changes in the cells. Investigation of the modulation of collagen gene expression may provide insights toward the understanding of the diseased lens capsule.
| Sawhney, R S (1993) Expression of type I and type III procollagen by lens epithelial cells. Invest Ophthalmol Vis Sci 34:2195-202 |
