Ru Y, Eyden B, Curry A, McWilliam L J, Coyne J D
Department of Histopathology, Christie Hospital NHS Trust, United Kingdom.
J Submicrosc Cytol Pathol. 2003 Jul;35(3):221-33.
Epithelial-myofibroblast transformation has been argued as playing a role in tubulo-interstitial fibrosis. To investigate this hypothesis, we examined 9 renal biopsy specimens from patients with chronic renal disease by light and electron microscopy. In all cases, electron microscopy confirmed light microscope observations in relation to tubulo-interstitial fibrosis-tubular atrophy, accumulation of extracellular matrix and of mesenchymal interstitial cells, and infiltration by inflammatory cells. Tubular epithelial cells (TECs) contained bundles of actin filaments: mostly lacking the focal densities typical of smooth-muscle myofilaments. The interstitium contained collagen and inflammatory cells. Some endothelial cells showed bundles of myofilaments. Free mesenchymal cells in the matrix were spindled and had sparse rough endoplasmic reticulum (rER), small attachment plaques, few actin filaments and no lamina. In one case, myofibroblasts (defined by abundant rER, myofilaments and fibronexuses) were present. Most of the mesenchymal cells, therefore, did not correspond to myofibroblasts, nor to classical fibroblasts because of the sparse rER and the presence of actin filaments. We therefore called these cells myoid stromal cells, regarding them as stromal mesenchymal elements showing partial activation towards a smooth-muscle phenotype. This paper demonstrates a greater phenotypic complexity of actin-containing stromal cells in the interstitium than previously appreciated, with only a minority conforming to true or fully differentiated myofibroblasts. The widespread presence of actin (as filaments or immunoreactivity) in both TECs and interstitial cells, combined with the absence of evidence of intermediate forms or of migration from epithelium into interstitium, may point to epithelium and interstitium as separate targets for actin upregulation as an alternative hypothesis to epithelial-myofibroblast transformation.
上皮-肌成纤维细胞转化被认为在肾小管间质纤维化中起作用。为了研究这一假说，我们通过光学显微镜和电子显微镜检查了9例慢性肾病患者的肾活检标本。在所有病例中，电子显微镜证实了光学显微镜观察到的肾小管间质纤维化——肾小管萎缩、细胞外基质和间充质间质细胞积聚以及炎性细胞浸润。肾小管上皮细胞（TECs）含有肌动蛋白丝束：大多缺乏平滑肌肌丝典型的粘着斑。间质含有胶原蛋白和炎性细胞。一些内皮细胞显示有肌丝束。基质中的游离间充质细胞呈纺锤形，粗面内质网（rER）稀少，附着斑小，肌动蛋白丝少且无基膜。在1例病例中，存在肌成纤维细胞（由丰富的rER、肌丝和纤维连接蛋白定义）。因此，大多数间充质细胞既不符合肌成纤维细胞，也不符合经典的成纤维细胞，因为rER稀少且存在肌动蛋白丝。我们因此将这些细胞称为类肌基质细胞，将它们视为向平滑肌表型显示部分活化的基质间充质成分。本文证明，间质中含肌动蛋白的基质细胞的表型复杂性比以前认识到的更大，只有少数符合真正的或完全分化的肌成纤维细胞。TECs和间质细胞中肌动蛋白（作为丝或免疫反应性）的广泛存在，加上缺乏中间形式或从上皮迁移到间质的证据，可能表明上皮和间质是肌动蛋白上调的独立靶点，这是上皮-肌成纤维细胞转化的另一种假说。
