Kim Y, Kleppel M M, Butkowski R, Mauer S M, Wieslander J, Michael A F
Department of Pediatrics, University of Minnesota, Minneapolis 55455.
Am J Pathol. 1991 Feb;138(2):413-20.
Diabetic nephropathy is characterized by progressive expansion of mesangial matrix and thickening of the glomerular basement membrane (GBM). Kidney tissues from 13 patients with insulin-dependent diabetes mellitus were studied by immunohistochemical techniques for the distribution of three recently described collagen peptides (M28+, M28 [Good-pasture antigen], and Alport antigen) and various components of classical type IV collagen [alpha 1(IV) noncollagenous (NC) globular domain, alpha 2(IV) NC, 7S, triple helix]. Recently M28 and M28+ were designated as NC monomers of alpha 3(IV) and alpha 4(IV) based on limited amino acid sequencing. During the course of the disease, the distribution of the M28 chains and the Alport peptide segregated completely from that of classical type IV collagen. In diabetic kidneys, antibodies to the M28 and Alport peptides reacted intensely with the thickened GBM but not with the mesangium. In contrast, the reactivity of antibodies to various components of classical type IV collagen was prominent within the expanded mesangial matrix with significant decrease in reactivity in the peripheral capillary wall. In hyalinized glomeruli, components of classical type IV collagen virtually disappeared, whereas the M28 and Alport peptides persisted in the collapsed GBM. These studies support the view that expansion of the mesangial matrix and thickening of the GBM involve separate and distinct collagen components. The differential expression of the M28 and Alport peptides compared with that of classical type IV collagen may be a consequence of differing sites of synthesis (classical type IV collagen from endothelial/mesangial cells and M28 and Alport chains from visceral epithelial cells), independent control mechanisms, and/or differences in degradation.
糖尿病肾病的特征是系膜基质进行性扩张和肾小球基底膜（GBM）增厚。采用免疫组织化学技术，对13例胰岛素依赖型糖尿病患者的肾组织进行研究，观察三种最近描述的胶原肽（M28 +、M28[古德帕斯丘抗原]和奥尔波特抗原）以及经典IV型胶原的各种成分[α1(IV)非胶原(NC)球状结构域、α2(IV) NC、7S、三螺旋]的分布情况。最近，基于有限的氨基酸测序，M28和M28 +被指定为α3(IV)和α4(IV)的NC单体。在疾病过程中，M28链和奥尔波特肽的分布与经典IV型胶原的分布完全分离。在糖尿病肾中，针对M28和奥尔波特肽的抗体与增厚的GBM强烈反应，但与系膜无反应。相反，针对经典IV型胶原各种成分的抗体反应在扩张的系膜基质中很突出，而在外周毛细血管壁中的反应性显著降低。在玻璃样变的肾小球中，经典IV型胶原成分几乎消失，而M28和奥尔波特肽仍存在于塌陷的GBM中。这些研究支持这样一种观点，即系膜基质的扩张和GBM的增厚涉及不同的胶原成分。与经典IV型胶原相比，M28和奥尔波特肽的差异表达可能是由于合成部位不同（经典IV型胶原由内皮/系膜细胞合成，M28和奥尔波特链由脏层上皮细胞合成）、独立的控制机制和/或降解差异所致。
