Rosenblum N D
Division of Nephrology, Children's Hospital, Harvard Medical School, Boston, Massachusetts.
Kidney Int Suppl. 1994 Feb;45:S73-7.
Mesangial sclerosis is a final common pathway to glomerular destruction in a variety of glomerular diseases. The expression of several classes of extracellular matrix (ECM) molecules has been defined in the normal and diseased mesangial matrix (MM). However, the manner in which these ECM components determine the three dimensional structure and function of the MM remains to be defined. Structural studies of the MM suggest that its constituent molecules are regionally organized into subcompartments with different three dimensional structures. The diversity of matrix molecules expressed within the MM as well as the organization of these components in nonrenal ECM's, such as the cornea, provides further support for this organizational model. The study of the cornea has also revealed that novel short chain collagenous proteins partially 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 glomerulus, and depending on its conformation, may serve unique functions. In the chronically diseased MM, normal MM components are overexpressed and fibrillar collagens are expressed de novo in a delayed fashion. Enhanced proteoglycan expression, observed early in disease, may determine increased volume of the mesangium. This, in turn, may stimulate the production of fibrillar collagens by mesangial cells resulting in a fibrillar noncompliant mesangial matrix.
系膜硬化是多种肾小球疾病中肾小球破坏的最终共同途径。在正常和患病的系膜基质（MM）中已明确了几类细胞外基质（ECM）分子的表达情况。然而，这些ECM成分决定MM三维结构和功能的方式仍有待确定。对MM的结构研究表明，其组成分子在区域上被组织成具有不同三维结构的亚区室。MM内表达的基质分子的多样性以及这些成分在非肾ECM（如角膜）中的组织方式，为这种组织模型提供了进一步的支持。对角膜的研究还表明，新型短链胶原蛋白质部分决定了基质的三维结构。最近，在系膜细胞和完整的肾小球中发现了一种新型胶原——VIII型胶原。据推测，VIII型胶原在肾小球内既以聚合物形式表达，也以单体形式表达，并且根据其构象可能发挥独特的功能。在慢性患病的MM中，正常MM成分过度表达，而纤维状胶原以延迟的方式重新表达。在疾病早期观察到的蛋白聚糖表达增强，可能决定系膜体积增加。这反过来可能刺激系膜细胞产生纤维状胶原，导致形成纤维状、顺应性差的系膜基质。
