Groma V
Laboratory of Electron Microscopy, Medical Academy of Latvia, Riga.
Nephrol Dial Transplant. 1998 Feb;13(2):305-12. doi: 10.1093/oxfordjournals.ndt.a027823.
Overproduction of collagenous fibres types I and III is a common finding of fibrotic injury. Collagen type VI is generally associated with type I. Appearance of fibroblasts expressing alpha-smooth muscle actin (ASMA) and their role in fibrogenesis has been partly defined. However, correlation between renal fibroblasts and accumulation of microfibrillar collagen type VI, as well as its exact distribution, is not fully delineated. This study was undertaken to investigate these issues using a complex morphological approach.
Morphological examination included immunohistochemical detection of the collagen type VI and ASMA, relying on a streptavidin-biotin-peroxidase-based technique, and electron microscopy.
Collagen type VI was strongly expressed in areas of fibrotic injury, although mild expression was always revealed in renal interstitium. Glomerular immunoreactivity with the anti-collagen type VI antibody was almost nil excepting cases of diabetic glomerulosclerosis and amyloid nephrosis. Glomerular nodules in cases of diabetes displayed intense reactivity. Mesangial, as well as discontinuous peripheral deposition of collagen along the glomerular basement membrane, was noticed in case of amyloidosis. Ultrastructurally, cross-banded collagen microfibrils were found in renal interstitium in close association with the fibroblast membrane. Moreover, fibrillar elements revealing tubular structure and fine filamentous material were observed between cross-banded microfibrils. Some of fibroblasts exhibited bundles of microfilaments in their cytoplasm. An increased number of ASMA-positive cells was detected in fibrotic interstitium. An intense concentric network made up of actin-bearing cells surrounded glomerular capillaries in the case of crescentic glomerular lesions.
Markedly increased deposition of collagen type VI takes place in renal fibrotic lesions. Simultaneously, interstitial fibrotic areas appeared to contain a great number of fibroblasts sharing morphological characteristics of classic fibroblasts and smooth muscle cells. Detailed examination of coexistence of these two interstitial phenomena should further clarify the cellular mechanisms involved in renal interstitial fibrosis.
I型和III型胶原纤维过度产生是纤维化损伤的常见表现。VI型胶原通常与I型相关。表达α-平滑肌肌动蛋白（ASMA）的成纤维细胞的出现及其在纤维化形成中的作用已部分明确。然而，肾成纤维细胞与VI型微纤维胶原积累之间的相关性及其确切分布尚未完全阐明。本研究采用复杂的形态学方法来探讨这些问题。
形态学检查包括基于链霉亲和素-生物素-过氧化物酶技术的VI型胶原和ASMA的免疫组织化学检测以及电子显微镜检查。
VI型胶原在纤维化损伤区域强烈表达，尽管在肾间质中始终显示轻度表达。除糖尿病性肾小球硬化和淀粉样变性肾病外，抗VI型胶原抗体的肾小球免疫反应性几乎为零。糖尿病病例中的肾小球结节显示出强烈的反应性。在淀粉样变性病例中，观察到系膜以及沿肾小球基底膜的胶原的不连续外周沉积。超微结构上，在肾间质中发现交叉带状胶原微纤维与成纤维细胞膜紧密相关。此外，在交叉带状微纤维之间观察到显示管状结构和细丝状物质的纤维成分。一些成纤维细胞在其细胞质中表现出微丝束。在纤维化间质中检测到ASMA阳性细胞数量增加。在新月体性肾小球病变的情况下，由含肌动蛋白的细胞组成的强烈同心网络围绕肾小球毛细血管。
VI型胶原在肾纤维化病变中的沉积明显增加。同时，间质纤维化区域似乎含有大量具有经典成纤维细胞和平滑肌细胞形态特征的成纤维细胞。对这两种间质现象共存的详细检查应进一步阐明参与肾间质纤维化的细胞机制。
