REGULATION OF THE RAT INTERSTITIAL COLLAGENASE PROMOTER BY IL-1-BETA,C-JUN, AND RAS-DEPENDENT SIGNALING IN GROWTH-PLATE CHONDROCYTES

Citation
Rm. Grumbles et al., REGULATION OF THE RAT INTERSTITIAL COLLAGENASE PROMOTER BY IL-1-BETA,C-JUN, AND RAS-DEPENDENT SIGNALING IN GROWTH-PLATE CHONDROCYTES, Journal of cellular biochemistry, 67(1), 1997, pp. 92-102
Citations number
51
Categorie Soggetti
Biology,"Cell Biology
ISSN journal
07302312
Volume
67
Issue
1
Year of publication
1997
Pages
92 - 102
Database
ISI
SICI code
0730-2312(1997)67:1<92:ROTRIC>2.0.ZU;2-V
Abstract
In an attempt to better define molecular influences on rat interstitia l collagenase gene expression in cartilage, the promoter function was characterized using transient transfection assay, electrophoresis mobi lity shift assay, and genetic analysis in isolated growth plate chondr ocytes. Data from 5'-flanking deletion and selected mutations suggest that multiple cis elements in both the proximal and distal regions of the promoter were important in the regulation of promoter activity. A proximal tumor response element (TRE) was shown to be necessary for ba sal and interleukin (IL)-1 beta-inducible reporter gene activity. Cell s stimulated by IL-1 beta (1 ng/ml; 18 h) had elevated TRE binding act ivity, and one of the factors involved was identified as the nuclear p rotein, c-Jun. Indeed, c-Jun directed antisense oligonucleotides reduc ed rat interstitial collagenase mRNA. A sense oligonucleotide was inef fective. Regulation of promoter activity was susceptible to Ras-depend ent signaling as expression of dominant negative mutant of Ras kinase (pZIP-RasN17) reduced reporter gene activity. in a comparison of proxi mal promoter reporter plasmid activity between proliferative and hyper trophic cells, inhibition of Ras-dependent signaling was less effectiv e in the later cell type. This study suggests that the activation of n uclear binding proteins that bind TRE may be a common event with IL-1 beta regulation. Moreover, these data suggest that the regulation of r at interstitial collagenase gene expression combinatorial process and multiple cis-acting regulatory sites may interact to exert different e ffects dependent on the stage of chondrocyte differentiation. (C) 1997 Wiley-Liss, Inc.