Actin filaments in human renal tubulo-interstitial fibrosis: significance for the concept of epithelial-myofibroblast transformation.
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.
Ru
Y
Y
Department of Histopathology, Christie Hospital NHS Trust, United Kingdom.
Eyden
B
B
Curry
A
A
McWilliam
L J
LJ
Coyne
J D
JD
D008841:Actin Cytoskeleton / Q000378:metabolism / Q000648:ultrastructure*; D002454:Cell Differentiation; D004847:Epithelial Cells / Q000378:metabolism / Q000473:pathology*; D005347:Fibroblasts / Q000378:metabolism / Q000648:ultrastructure*; D005355:Fibrosis / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D007684:Kidney Tubules / Q000378:metabolism / Q000473:pathology*; D008854:Microscopy, Electron; D008856:Microscopy, Fluorescence; D009395:Nephritis, Interstitial / Q000378:metabolism / Q000473:pathology*