Regulation of extracellular matrix production by chemically synthesized subfragments of type I collagen carboxy propeptide.
The complete COOH-propeptide of human alpha 1(I) procollagen was chemically synthesized as a series of overlapping subfragments which were then tested for their effect on extracellular matrix protein production by subconfluent human lung fibroblasts (HFL-1). One peptide (R11; residues 197-241) stimulated production of both collagen and fibronectin by 6-8-fold while a second peptide with a partial overlap with R11 (R9; residues 182-216) enhanced collagen accumulation. The peptide R12 (residues 197-216), which has a sequence common to both R9 and R11, also stimulated collagen production, suggesting that this 20-residues peptide alone contains the required structure for activity. The other synthetic peptides, R1-R13, were inactive in their ability to alter collagen or fibronectin production. Consistent with previously published data, the COOH-terminal peptide, R14, inhibited extracellular matrix production [Aycock, R.A., Raghow, R., Stricklin, G.P., Seyer, J.M., & Kang, A.H. (1986) J. Biol. Chem. 261, 14355-14360]. Both R9 and R11 preferentially stimulated production of collagen types I and III and fibronectin in dose-dependent manner. Elevated collagen and fibronectin production was evident at 4-h posttreatment, and maximal enhancement was seen at 8 h after exposure to peptides. Interestingly, subconfluent cultures of HFL-1 fibroblasts responded vigorously to the stimulatory action of R9 and R11 while confluent cells failed to show any response. Steady-state levels of messenger RNAs encoding type I procollagen and fibronectin were not measurably altered by treatment with R9 or R11, suggesting that the regulation of procollagens and fibronectin by these peptides involves posttranscriptional mechanisms.(ABSTRACT TRUNCATED AT 250 WORDS)
Katayama
K
K
Veterans Affairs Medical Center, Research Service, Memphis, TN 38104.
Seyer
J M
JM
Raghow
R
R
Kang
A H
AH
D000595:Amino Acid Sequence; D002478:Cells, Cultured; D003094:Collagen / Q000138:chemical synthesis / Q000502:physiology*; D004247:DNA / Q000096:biosynthesis; D004591:Electrophoresis, Polyacrylamide Gel; D005109:Extracellular Matrix / Q000378:metabolism*; D016326:Extracellular Matrix Proteins / Q000096:biosynthesis; D005353:Fibronectins / Q000032:analysis; D006801:Humans; D008168:Lung / Q000378:metabolism; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000138:chemical synthesis / Q000502:physiology; D011347:Procollagen / Q000138:chemical synthesis / Q000502:physiology*; D012323:RNA Processing, Post-Transcriptional; D012333:RNA, Messenger / Q000032:analysis; D012689:Sequence Homology, Nucleic Acid
D016326:Extracellular Matrix Proteins; D005353:Fibronectins; D010446:Peptide Fragments; D011347:Procollagen; D012333:RNA, Messenger; D003094:Collagen; D004247:DNA