THE MESANGIAL MATRIX IN THE NORMAL AND SCLEROTIC GLOMERULUS

Mesangial sclerosis is a final common pathway to glomerular destructio n in a variety of glomerular diseases. The expression of several class es of extracellular matrix (ECM) molecules has been defined in the nor mal and diseased mesangial matrix (MM). However, the manner in which t hese ECM components determine the three dimensional structure and func tion of the MM remains to be defined. Structural studies of the MM sug gest that its constituent molecules are regionally organized into subc ompartments with different three dimensional structures. The diversity of matrix molecules expressed within the MM as well as the organizati on of these components in nonrenal ECM's, such as the cornea, provides further support for this organizational model. The study of the corne a has also revealed that novel short chain collagenous proteins partia lly determine the three dimensional structure of the matrix. Recently, a novel collagen, type VIII collagen, has been described in mesangial cells and in the intact glomerulus. It is hypothesized that type VIII collagen is expressed both as a polymer and as a monomer within the g lomerulus, and depending on its conformation, may serve unique functio ns. In the chronically diseased MM, normal MM components are overexpre ssed and fibrillar collagens are expressed de novo in a delayed fashio n. Enhanced proteoglycan expression, observed early in disease, may de termine increased volume of the mesangium. This, in turn, may stimulat e the production of fibrillar collagens by mesangial cells resulting i n a fibrillar noncompliant mesangial matrix.