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The progression of renal diseases: On the pathogenesis of renal interstitial fibrosis

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Summary

Renal interstitial fibrosis (RIF) frequently occurs in inflammatory and non-inflammatory kidney diseases and is associated with a decline in renal excretory function. Fibroblasts which occupy the renal interstitium are involved mainly in the formation of RIF not only by the production of extracellular matrix, but also by regulatory processes. They respond to a variety of cytokines released by different cell types. To investigate mechanisms leading to RIF, immunohistochemical analysis and cell cultures of renal biopsies in various renal diseases have been performed. T lymphocytes are the major cells infiltrating the renal interstitium, and their number correlates with the impairment of renal function. In most forms of glomerulonephritis accompanied by interstitial inflammation, an abnormal expression of HLA-DQ/-DP molecules, frequently associated with an aberrant expression of the intercellular adhesion molecule 1 (ICAM-1), was observed on proximal tubular epithelial cells, indicating that these cells may play a role in antigen presentation. The cell biological experiments revealed the presence of the three mitotic fibroblast types (MFI-MFIII) and the three postmitotic types (PMFIV-PMFVI) in the cell culture. The number of fibroblasts in primary and passage-1 culture was increased sevenfold in cultures derived from kidneys with RIF (FKIF cells) in comparison to normal kidneys (NKF cells). FKIF cells show hyperproliferative growth and synthesize an increased amount of total collagen, especially types III and V. These cells express a protein, named “FIBROSIN”, which seems to be specific for FKIF cells. Further extended cell biological analyses are currently being performed to investigate interactions of tubular cells, lymphocytes, macrophages, and fibroblasts in order to shed more light on the pathomechanisms involved in fibrogenesis leading to renal interstitial fibrosis.

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Abbreviations

AG:

antigen

DMEM:

Dulbecco's modified Eagle's medium

ECM:

extracellular matrix

FACS:

fluorescence activated cell sorter

FGF:

fibroblast growth factor

FKIF:

fibroblast derived from kidneys with interstitial fibrosis

FSGS:

focal segmental glomerulosclerosis

GBM:

glomerular basement membrane

GM-CSF:

granulocyte/macrophage-colony stimulating factor

GN:

glomerulonephritis

HLA:

human leukocyte antigen

ICAM-1:

intercellular adhesion molecule 1

ICI:

interstitial cellular infiltrate

IgA N:

immunoglobulin A nephropathy

IL:

interleukin

INF-γ :

interferon gamma

LFA:

leukocyte function antigen

M-CSF:

macrophage-colony stimulating factor

MF:

mitotic fibroblast

MGN:

membranous glomerulonephritis

MesPrGN:

mesangioproliferative glomerulonephritis

MHC:

major histocompatibility complex

Min Ch:

minimal changes

Min Les:

minor lesions

MMC:

mitomycin C

MPGN:

membranoproliferative glomerulonephritis

NKF:

normal kidney fibroblast

NSF:

normal skin fibroblast

PDGF:

platelet-derived growth factor

PMF:

postmitotic fibroblast

PTEC:

proximal tubular epithelial cells

TGF:

transforming growth factor

TNF:

tumor necrosis factor

RIF:

renal interstitial fibrosis

RPGN:

rapidly progressive glomerulonephritis

TBM:

tubular basement membrane

TCR:

T-cell receptor

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Authors and Affiliations

  1. Medizinische Universitätsklinik, Abt. 3, Eberhard-Karls-Universität, Tübingen

    G. A. Müller & J. Markovic-Lipkovski

  2. Entwicklungsbiologie, SFB 223, Universität Bielefeld, Deutschland

    H. P. Rodemann

Authors
  1. G. A. Müller
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  2. J. Markovic-Lipkovski
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  3. H. P. Rodemann
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Additional information

Preprint of a lecture to be read at the 22nd Congress of the “Gesellschaft für Nephrologie”, Heidelberg, September 15–18, 1991 (Editor: Prof. Dr. E. Ritz, Heidelberg)

Supported by the Deutsche Forschungsgemeinschaft DFG Mu 523/3-5, SFB 223, Project B5/Ro 527/2-2 and by the Alexander von Humboldt-Stiftung

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Müller, G.A., Markovic-Lipkovski, J. & Rodemann, H.P. The progression of renal diseases: On the pathogenesis of renal interstitial fibrosis. Klin Wochenschr 69, 576–586 (1991). https://doi.org/10.1007/BF01649320

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