Differential extracellular matrix gene expression by fibroblasts during their proliferative life span in vitro and at senescence. Academic Article Article uri icon

Overview

MeSH

  • Animals
  • Blotting, Northern
  • Cell Count
  • Cell Division
  • Cell Survival
  • Cells, Cultured
  • Cricetinae
  • DNA Probes
  • Fibronectins
  • Mesocricetus
  • Procollagen
  • RNA, Messenger
  • Skin
  • Skin Physiological Phenomena
  • Time Factors

MeSH Major

  • Aging
  • Extracellular Matrix Proteins
  • Fibroblasts
  • Gene Expression

abstract

  • Increasing evidence supports the idea that the finite proliferative life span of normal fibroblasts is a differentiation-like phenomenon. If this were correct, an ordered sequence of differential gene expression should be associated with the in vitro progression of cells from low passage to high passage (senescence). To define the pattern of expression of fibroblast differentiation-associated genes during this in vitro progression, we have determined the temporal pattern of expression of extracellular matrix (ECM) genes in Syrian hamster dermal fibroblasts as a function of passage level and percentage of proliferative life span in vitro. Steady-state mRNA levels were determined by Northern and dot blot analyses of total cellular RNA hybridized with cDNA probes specific for fibronectin, procollagen alpha 1III, and procollagen alpha 1I. Cells were analyzed at 24 hr postconfluence to minimize the presence of actively proliferating cells, and because maximal levels of fibronectin, alpha 1III, and alpha 1I mRNAs were observed 24 hr postconfluence. Unique, multiphasic patterns of expression of each of these ECM components were observed as the cells progressed from low passage to high passage. As the cells reached midhigh passage, fibronectin mRNA levels increased. This midpassage increase in fibronectin was followed by an increase in the level of alpha 1III mRNA as the cells reached the end of their in vitro proliferative life span, and then alpha 1I when the cells entered the postmitotic senescent phase, at which time the level of fibronectin mRNA also declined. A similar overlapping cascade pattern of up-regulation of these genes is seen during development and wound repair. This suggests that as cultured fibroblasts reach the end of their proliferative life span, they reinitiate a gene expression program used in tissue development and repair.

publication date

  • April 1992

has subject area

  • Aging
  • Animals
  • Blotting, Northern
  • Cell Count
  • Cell Division
  • Cell Survival
  • Cells, Cultured
  • Cricetinae
  • DNA Probes
  • Extracellular Matrix Proteins
  • Fibroblasts
  • Fibronectins
  • Gene Expression
  • Mesocricetus
  • Procollagen
  • RNA, Messenger
  • Skin
  • Skin Physiological Phenomena
  • Time Factors

Research

keywords

  • Comparative Study
  • Journal Article

Identity

Language

  • eng

Digital Object Identifier (DOI)

  • 10.1002/jcp.1041510119

PubMed ID

  • 1560040

Additional Document Info

start page

  • 147

end page

  • 155

volume

  • 151

number

  • 1