Elastic fiber proteins in the glomerular mesangium in vivo and in cell culture

Kidney Int. 2000 Oct;58(4):1588-602. doi: 10.1046/j.1523-1755.2000.00320.x.

Abstract

Background: Glomerular capillaries of the mammalian kidney are exposed to high intraluminal hydrostatic pressures and require elastic constraint to maintain size, shape, and integrity. Previous morphological and functional studies indicated that the extracellular matrices of glomeruli, that is, basement membrane and mesangial matrix, contribute to glomerular resilience and mechanical stability. Immunofluorescence microscopy findings demonstrated elastic fiber components to be located in the renal vasculature, including glomeruli. The aim of this study was to clarify the exact glomerular localization, composition, and cellular production of these proteins.

Methods: We examined the renal distribution of the elastic fiber proteins fibrillin-1, emilin, microfibril-associated glycoproteins (MAGPs) 1 and 2, latent transforming growth factor-binding protein-1 (LTBP-1), and elastin using immunohistology and immunoelectron microscopy of human, rat, and mouse kidneys. In mesangial cell cultures, we also studied the expression and extracellular deposition of such proteins by use of Northern blotting and immunocytochemistry.

Results: Fibrillin-1, emilin, MAGPs 1 and 2, and LTBP-1 were present in glomeruli of mouse, rat, and human kidney, where they were located predominantly in the mesangial extracellular matrix underlying glomerular endothelium and basement membrane. Several of these proteins, as well as elastin, were also expressed in the renal vasculature. While elastin localized to the glomerular vascular pole in afferent and efferent arterioles extending to Bowman's capsule, it was not found in the glomerular capillary tuft. Cultured mesangial cells of rat, mouse, and human kidneys expressed mRNAs of fibrillin-1, emilin, MAGP-2, and elastin, and the respective proteins localized within and outside of mesangial cells, as shown by immunocytochemistry. mRNA expression of fibrillin-1, emilin, and elastin was strong in quiescent mesangial cells; their gene expression was further up-regulated by transforming growth factor-beta1, while it was transiently reduced when cells were exposed to mitogenic 10% fetal calf serum and platelet-derived growth factor.

Conclusions: These findings demonstrate that specific elastic fiber proteins are produced and secreted by mesangial cells. This process is regulated by growth factors. Their abundance in the extracellular matrix of the mesangium is in keeping with the concept that elastic fiber proteins contribute to the mechanical stability and elastic strength of the glomerular capillary tuft.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anticoagulants / pharmacology
  • Becaplermin
  • Carrier Proteins / analysis
  • Carrier Proteins / genetics
  • Cells, Cultured
  • Contractile Proteins / analysis
  • Contractile Proteins / genetics*
  • Elasticity
  • Elastin / analysis
  • Elastin / genetics
  • Epithelial Cells / chemistry
  • Epithelial Cells / physiology
  • Epithelial Cells / ultrastructure
  • Extracellular Matrix / chemistry
  • Extracellular Matrix / physiology
  • Extracellular Matrix Proteins*
  • Fibrillin-1
  • Fibrillins
  • Fluorescent Antibody Technique
  • Gene Expression / drug effects
  • Gene Expression / physiology
  • Glomerular Mesangium / blood supply
  • Glomerular Mesangium / cytology*
  • Glomerular Mesangium / physiology*
  • Homeostasis / physiology
  • Humans
  • Hydrostatic Pressure
  • Intracellular Signaling Peptides and Proteins*
  • Latent TGF-beta Binding Proteins
  • Male
  • Membrane Glycoproteins / analysis
  • Membrane Glycoproteins / genetics
  • Mice
  • Microcirculation / physiology
  • Microfilament Proteins / analysis
  • Microfilament Proteins / genetics*
  • Microscopy, Immunoelectron
  • Platelet-Derived Growth Factor / pharmacology
  • Proto-Oncogene Proteins c-sis
  • RNA Splicing Factors
  • RNA, Messenger / analysis
  • Rats
  • Transforming Growth Factor beta / pharmacology

Substances

  • Anticoagulants
  • Carrier Proteins
  • Contractile Proteins
  • Extracellular Matrix Proteins
  • FBN1 protein, human
  • Fbn1 protein, mouse
  • Fbn1 protein, rat
  • Fibrillin-1
  • Fibrillins
  • Intracellular Signaling Peptides and Proteins
  • LTBP1 protein, human
  • Latent TGF-beta Binding Proteins
  • Ltbp1 protein, mouse
  • Membrane Glycoproteins
  • Microfilament Proteins
  • Platelet-Derived Growth Factor
  • Proto-Oncogene Proteins c-sis
  • RNA Splicing Factors
  • RNA, Messenger
  • Transforming Growth Factor beta
  • elastin microfibril interface located protein
  • microfibrillar protein
  • Becaplermin
  • Elastin