The spatial and temporal expression of extracellular matrix proteins and their receptors are critical for normal tissue organization, development, and growth. Conversely, abnormal expression of these extracellular proteins and receptors as a result of either genetic or acquired diseases often represents the pathologic basis for clinical illness. For example, many renal, pulmonary, hepatic, and skin diseases are characterized by abnormal deposition of extracellular matrix proteins leading to impaired function and healing. The purpose of these studies is to understand the molecular mechanisms by which genes for the extracellular matrix proteins and their receptors are regulated during normal development and in disease. Using a combination of molecular, cellular, and physiologic techniques, we are evaluating normal and pathologic conditions associated with changes in the expression of extracellular matrix proteins and their receptors including normal fetal development, disordered renal growth typical of polycystic kidney disease and cancers of the kidney, and the increase in extracellular matrix proteins observed in diabetic nephropathy, cyclosporine toxicity, and with retroviral infections. We are currently evaluating matrix gene expression in an attempt to identify important transcriptional factors during development and disease; we are exploring the specific peptide sequences of matrix proteins which are necessary for renal cell attachment, differentiation, and cell function; and we are creating transgenic mice in order to evaluate the importance of tissue-specific gene expression which may contribute to the clinical manifestations of disease.
