Differential extracellular matrix gene expression by fibroblasts during their proliferative life span in vitro and at senescence

Augustine M.K. Choi, David R. Olsen, Keith G. Cook, Scott F. Deamond, Jouni Uitto, Sarah A. Bruce

Research output: Contribution to journalArticle

31 Scopus citations

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 α1 III, and procollagen α1 I. Cells were analyzed at 24 hr postconfluence to minimize the presence of actively proliferating cells, and because maximal levels of fibronectin, α1 III, and α1 I 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 α1 III mRNA as the cells reached the end of their in vitro proliferative life span, and then α1 I when the cells entered the postmitotic senescert 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. © 1992 Wiley‐Liss, Inc.

Original languageEnglish (US)
Pages (from-to)147-155
Number of pages9
JournalJournal of Cellular Physiology
Volume151
Issue number1
DOIs
StatePublished - Apr 1992

ASJC Scopus subject areas

  • Physiology
  • Clinical Biochemistry
  • Cell Biology

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