Abstract
The NH2 and COOH propieces of fibril-forming collagens are cleaved off extracellularly and have been implicated in feedback regulation of their own synthesis. Recently, we showed that a subfragment of the carboxyl-terminal propeptide of type I collagen (residues 197-241) dramatically augments extracellular matrix production in subconfluent fibroblasts. This stimulation of type I collagen, type III collagen, and fibronectin production occurred in a dose- and time-dependent manner with no effect on total protein synthesis or on the ratio of secreted proteins to cell-associated proteins (Katayama, K., Seyer, J.M., Raghow, R., and Kang, A.H. (1991) Biochemistry 30, 7097-7104). In the present report, we have extensively dissected this subfragment of the propeptide and found that the pentapeptide Lys-Thr-Thr-Lys-Ser (residues 212-216) is the minimum sequence necessary for potent stimulation of collagen and fibronectin production in a variety of mesenchymal cells. We postulate that the extracellular matrix production in fibroblasts may be subject to either positive or negative feedback regulation depending on the repertoire of specific proteases during postinflammatory tissue regeneration and fibrosis.
Highlights
As described previously [11,12], none of the peptides except R14 inhibited collagen synthesis, but to Extracellular Matrix Production* oursurprise, two overlappingpeptidesnamed R9 and R11
11 Biochemistry, University of Tennessee, Memphis, Tennessee 38104 and the llveterans Administration Medical Center, Memphis, Tennessee38104 strongly stimulated collagen productioninhumanlungfibroblasts.The stimulatory effect of these peptides on type I and type 111 collagen and fibronectin productionwas maximal in subconfluent cells and was completely abolished as thecells became confluent [12]
The NH, and COOH propieces of fibril-forming collagens are cleaved off extracellularly and have been implicated in feedback regulation of their own synthesis.,Recently, we showed that a subfragment of the carboxyl-terminal propeptide of type I collagen dramatically augments extracellular matrix production in subconfluent fibroblasts
Summary
Tent stimulation of collagen and fibronectin production in a variety of mesenchymal cells. We postulate that the extracellular matrix production in fibroblasts may be subject toeither positive or negative feedback regulation depending on the repertoire of specific proteases during postinflammatory tissue regeneration and fibrosis. T o define the minimum regulatory sequence, we chemically acetic acid They were desalted by gel filtration with Sephadex G-25 synthesized a series of overlapping peptides encompassing thecolumns using 0.1 M acetic acid and 20% acetonitrile as the eluting entire COOH propeptidoef pro-al[1] collagen and tested their solvent and purified by HPLC on a Vydac 218TP54 C18 column(The. J. CellCulture-Humanlung fibroblasts (HFL-1, passages11-20) were maintained in Dulbecco’smodifiedEagle’smedium (DMEM).
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