Lefty contributes to the remodeling of extracellular matrix by inhibition of connective tissue growth factor and collagen mRNA expression and increased proteolytic activity in a fibrosarcoma model

James M. Mason, Hao Peng Xu, Srinivasa K. Rao, Andrew Leask, Michele Barcia, Jidong Shan, Robert Stephenson, Siamak Tabibzadeh

Research output: Contribution to journalArticle

26 Citations (Scopus)

Abstract

Homeostasis of the extracellular matrix (ECM) of tissues is regulated by controlling deposition and degradation of ECM proteins. The breakdown of ECM is essential in blastocyst implantation and embryonic development, tissue morphogenesis, menstrual shedding, bone formation, tissue resorption after delivery, and tumor growth and invasion. TGF-β family members are one of the classes of proteins that actively participate in the homeostasis of ECM. Here, we report on the effect of lefty, a novel member of the TGF-β family, on the homeostasis of extracellular matrix in a fibrosarcoma model. Fibroblastic cells forced to express lefty by retroviral transduction lost their ability to deposit collagen in vivo. This event was associated with down-regulation of the steady-state level of connective tissue growth factor that induces collagen type I mRNA. In addition, lefty transduction significantly decreased collagen type I mRNA expression and simultaneously increased collagenolytic, gelatinolytic, elastolytic, and caseinolytic activities in vivo by the transduced fibroblasts. These findings provide a new insight on the actions of lefty and suggest that this cytokine plays an active role in remodeling of the extracellular matrix in vivo.

Original languageEnglish (US)
Pages (from-to)407-415
Number of pages9
JournalJournal of Biological Chemistry
Volume277
Issue number1
DOIs
StatePublished - Jan 4 2002
Externally publishedYes

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Connective Tissue Growth Factor
Fibrosarcoma
Extracellular Matrix
Collagen
Tissue
Collagen Type I
Messenger RNA
Homeostasis
Extracellular Matrix Proteins
Fibroblasts
Tumors
Bone
Deposits
Aptitude
Cytokines
Degradation
Morphogenesis
Osteogenesis
Embryonic Development
Down-Regulation

ASJC Scopus subject areas

  • Biochemistry

Cite this

Lefty contributes to the remodeling of extracellular matrix by inhibition of connective tissue growth factor and collagen mRNA expression and increased proteolytic activity in a fibrosarcoma model. / Mason, James M.; Xu, Hao Peng; Rao, Srinivasa K.; Leask, Andrew; Barcia, Michele; Shan, Jidong; Stephenson, Robert; Tabibzadeh, Siamak.

In: Journal of Biological Chemistry, Vol. 277, No. 1, 04.01.2002, p. 407-415.

Research output: Contribution to journalArticle

Mason, James M. ; Xu, Hao Peng ; Rao, Srinivasa K. ; Leask, Andrew ; Barcia, Michele ; Shan, Jidong ; Stephenson, Robert ; Tabibzadeh, Siamak. / Lefty contributes to the remodeling of extracellular matrix by inhibition of connective tissue growth factor and collagen mRNA expression and increased proteolytic activity in a fibrosarcoma model. In: Journal of Biological Chemistry. 2002 ; Vol. 277, No. 1. pp. 407-415.
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