Mechanisms of Progressive Renal Disease in Glomerulonephritis

doi:10.1016/S0272-6386(12)80971-1

American Journal of Kidney Diseases

Volume 23, Issue 2, February 1994, Pages 193-198

https://doi.org/10.1016/S0272-6386(12)80971-1 Get rights and content

Progressive renal disease in glomerulonephritis (GN) involves both glomerular and interstitial processes. In the glomerulus, sclerosis occurs with progressive accumulation of extracellular matrix components that reduce filtration surface area. In the interstitium, early inflammatory changes accompany GN with later development of fibrosis and tubular atrophy. Our studies have focused on the role of early cellular events in the development of glomerular and interstitial fibrosis. In the antithymocyte serum (ATS) model of mesangial proliferative GN, mesangial cell proliferation is initiated by processes involving complement and platelets and may involve basic fibroblast growth factor (bFGF). Mesangial cell proliferation is maintained by an autocrine mechanism involving upregulation of mesangial cell PDGF and PDGF receptors. Mesangial cells also change phenotype with expression of a-smooth muscle actin and production of type I collagen. These early changes precede upregulation of genes for the production of extracellular matrix components and the development of mesangial matrix expansion and sclerosis. Matrix expansion is reduced by factors that block cell proliferation, including platelet and complement depletion, heparin, and antibody to PDGF. A similar sequence of early platelet infiltration, increased expression of PDGF, and mesangial cell proliferation occurs early in the development of glomerulosclerosis in the remnant kidney model, and mesangial cell proliferation is a prominent early feature of experimental diabetic nephropathy. We believe these early glomerular cellular changes are linked to the later development of sclerosis. In the interstitium, acute GN is accompanied by upregulation of mRNA and protein for osteopontin, a macrophage chemotactic/adhesive factor expressed by cortical tubules following several types of glomerular injury. Interstitial macrophage localization occurs in areas of osteopontin expression followed by the development of interstitial fibrosis. These studies of early cellular events in the development of both glomerular and interstitial fibrosis may provide important clues to the mechanisms that underlie progressive renal disease in GN.

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^*: Supported by research grants from the United States Public Health Service (DK 34198, DK 43422, DK 02142, and DK 07467) and the Northwest Kidney Foundation.

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Mechanisms of Progressive Renal Disease in Glomerulonephritis*

Classification and treatment. Am J Kidney Dis

Am J Med

Kidney Int

Kidney Int

Kidney Int

Kidney Int

Kidney Int

Am J Kidney Dis

The progression of renal disease

N Engl J Med

Factors involved in the regulation of mesangial cell proliferation in vitro and in vivo

Kidney Int

Is mesangial cell proliferation required for extracellular matrix expansion in glomerular disease?

Contrib Nephrol

Does extracellular matrix expansion in glomerular disease require mesangial cell proliferation?

Kidney Int

Extracellular matrix gene expression in experimental glomerulonephritis

Curr Opin Nephrol Hypertens

Interactions of inflammatory and glomerular cells in the response to glomerular injury

Mesangial cells in the pathogenesis of progressive glomerular disease in animal models

Klin Wochenschr

Platelets mediate glomerular cell proliferation in immune complex nephritis in the rat induced by anti-mesangial cell antibodies

Am J Pathol

Platelet-complement interactions in mesangial proliferative nephritis in the rat

Am J Pathol

Rat glomerular mesangial cell synthesize basic FGF: Release, upregulated synthesis and mitogenicity in mesangial proliferative glomerulonephritis

J Clin Invest

Expression of smooth muscle cell phenotype by rat mesangial cell in immune complex nephritis

J Clin Invest

The activated mesangial cell: A glomerular myofibroblast

J Am Soc Nephrol

Platelet-derived growth factor (PDGF) and PDGF receptor are induced in mesangial proliferative nephritis in the rat

Proc Natl Acad Sci USA