Apoptosis and extracellular matrix-cell interactions in kidney disease

H. Makino, H. Sugiyama, N. Kashihara

Research output: Contribution to journalReview article

60 Citations (Scopus)

Abstract

Extracellular matrix (ECM)-cell interactions have major effects on phenotypic features such as cell growth, differentiation, and gene expression. Apoptosis is an active form of cell death that is crucial for maintaining an appropriate number of cells as well as tissue organization. Recent reports have implied that ECM can influence survival and apoptosis of several cell lineages including glomerular mesangial cells (MC). Numerous glomerular diseases are associated with the expansion of the mesangial ECM, which may eventually produce glomerular scarring. Glomerular cell apoptosis is associated with the deletion of glomerular cells and the accumulation of ECM in the progression of glomerulosclerosis in rat remnant kidney model induced by 5/6 nephrectomy. Our recent study indicated that basement membrane matrix (a model for normal ECM components) prevented cultured MC from undergoing apoptosis after serum deprivation, thus promoting their survival, compared with type I collagen matrix (a model for abnormal ECM components). Inhibition of matrix-derived signals by antisense oligonucleotides against β1 integrin increased MC apoptosis. Data suggest that the survival and death of MC are regulated by the surrounding ECM through integrin molecules. The mechanism of regulation of MC apoptosis by ECM requires further in vivo study to gain new insight into the treatment of glomerular diseases as well as the pathophysiology of the mesangium. Diabetic nephropathy is characterized by the abnormal ECM accumulation and the phenotypic change of MC. Some speculations on the possible involvement of apoptosis in diabetic nephropathy are also discussed.

Original languageEnglish
Pages (from-to)S67-S75
JournalKidney International, Supplement
Volume58
Issue number77
Publication statusPublished - Jan 1 2000

Keywords

  • Advanced glycation end products
  • Cell death
  • Diabetes
  • Diabetic nephropathy
  • Glomerulosclerosis
  • High glucose
  • Mesangial cell
  • Survival

ASJC Scopus subject areas

  • Nephrology

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