Demonstration of collagen type VI and alpha-smooth muscle actin in renal fibrotic injury in man

Abstract

Background: 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.

Methods: Morphological examination included immunohistochemical detection of the collagen type VI and ASMA, relying on a streptavidin-biotin-peroxidase-based technique, and electron microscopy.

Results: 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.

Conclusions: 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.