The renal interstitial compartment, situated between basement membranes of epithelia and vessels, contains two contiguous cellular networks. One network is formed by interstitial Wbroblasts, the second one by dendritic cells. Both are in intimate contact with each other. Fibroblasts are interconnected by junctions and connected to basement membranes of vessels and tubules by focal adhesions. Fibroblasts constitute the “skeleton” of the kidney. In the renal cortex, Wbroblasts produce erythropoietin and are distinguished from other interstitial cells by their prominent F-actin cytoskeleton, abundance of rough endoplasmic reticulum, and by ecto-5-nucleotidase expression in their plasma membrane. The resident dendritic cells belong to the mononuclear phagocyte system and fulWl a sentinel function. They are characterized by their expression of MHC class II and CD11c. The central situation of Wbroblasts suggests that signals from tubules, vessels, and inXammatory cells converge in Wbroblasts and elicit an integrated response. Following tubular damage and inXammatory signals Wbroblasts proliferate, change to the myoWbroblast phenotype and increase their collagen production, potentially resulting in renal Wbrosis. The acquisition of a proWbrotic phenotype by Wbroblasts in renal diseases is generally considered a main causal event in the progression of chronic renal failure. However, it might also be seen as a repair process.

In all parenchymal organs, including the kidney, the interstitium is situated in the space between the basement membranes of the epithelial cells and of the nutritive capillaries. This compartment is of eminent functional relevance in the healthy and diseased kidney. The Wbroblasts in the interstitium provide the “skeleton” of the tissue and maintain the three-dimensional architecture of the tissue. The interstitium is necessarily involved in all intrarenal exchange processes since the reabsorption and secretion of Xuid and solutes implicates a transit across the interstitial compartment. Cortical Wbroblasts play a role in the production of regulatory substances, such as extracellular adenosine (Le Hir and Kaissling 1993) and erythropoietin. In the healthy organ dendritic cells, belonging to the mononuclear phagocyte system, reside in the interstitium in line with their sentinel function. In disease, various inXammatory cells inWltrate the interstitium. In the diseased kidney, the cellular content as well as the content of Wbers and matrix in the interstitium increases, eventually yielding renal Wbrosis. The cortical interstitium, and in particular the Wbroblasts, are often overlooked in conventional tissue preparations of healthy kidneys. However, under inXammatory conditions the interstitial space becomes massively expanded and Wbroblasts acquire the myoWbroblast phenotype: they express alpha smooth muscle actin (SMA) and have an increased capacity for production of collagen Wbrils and matrix.

In this review based on studies in rats and mice we describe the morphology of interstitial cells of the healthy renal cortex and in various models of diseases. The observations suggest that Wbroblasts are the pivotal cells in the renal interstitium.

Following older electron microscopic investigations, only a few reports dealt with the structure of interstitial cells in healthy kidney. The reasons are mostly technical. The study of the cells in the cortical interstitium is diYcult since after immersion Wxation the interstitial space and the capillaries are usually collapsed whereas tubules are swollen. The light microscopic distinction between Wbroblasts, endothelial cells, and dendritic cells is awkward in such tissue preparations. Only perfusion Wxation and the use of thin light microscopic sections and of electron microscopy provide a reasonably safe distinction of Wbroblasts and other interstitial cells.

The cortical Wbroblasts contribute essentially to renal functions, not only as skeleton of the organ but also by producing regulatory substances such as, e.g. adenosine and erythropoietin. In response to tubular lesions Wbroblasts proliferate and transform into myoWbroblasts, thus initiating Wbrosis. The role of that process in renal diseases remains to be elucidated. On one hand, Wbrosis might contribute to the deterioration of renal function. On other hand, in the same way as in other organs, Wbrosis in the kidney might contribute to repair by containing inXammation and by preserving the organ architecture. Experimental models in which Wbrosis is induced by lesions to speciWc tubular cell types appear particularly promising for the study of the cross-talk between tubular cells and interstitial cells in disease.

Journal of Nephrology and Urology is an Open Access peer-reviewed publication that discusses current research and advancements in diagnosis and management of kidney disorders as well as related epidemiology, pathophysiology and molecular genetics.

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Regards
Maya Wilson
Editorial Assistant
Journal of Nephrology and Urology