Regulation of Extracellular Matrix Production by Chemically Synthesized Subfragments of Type I Collagen Carboxy Propeptide

Kou Katayama, Jerome M. Seyer, Rajendra Raghow, Andrew Kang

Research output: Contribution to journalArticle

42 Citations (Scopus)

Abstract

The complete COOH-propeptide of human α1(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 Rll, also stimulated collagen production, suggesting that this 20-residue 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. Finally, we observed that both R9 and R11 inhibited serum-induced stimulation of DNA synthesis in cells grown under serum-deprived conditions. Possible molecular mechanisms by which COOH-terminal peptide fragments regulate cellular proliferation and extracellular matrix biogenesis are considered.

Original languageEnglish (US)
Pages (from-to)7097-7104
Number of pages8
JournalBiochemistry
Volume30
Issue number29
DOIs
StatePublished - Jul 1 1991

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Collagen Type I
Extracellular Matrix
Fibronectins
Peptides
Collagen
Procollagen
Fibroblasts
Peptide Fragments
Collagen Type III
Extracellular Matrix Proteins
Serum
Cell culture
Cells
Cell Proliferation
Lung
Messenger RNA
DNA

All Science Journal Classification (ASJC) codes

  • Biochemistry

Cite this

Regulation of Extracellular Matrix Production by Chemically Synthesized Subfragments of Type I Collagen Carboxy Propeptide. / Katayama, Kou; Seyer, Jerome M.; Raghow, Rajendra; Kang, Andrew.

In: Biochemistry, Vol. 30, No. 29, 01.07.1991, p. 7097-7104.

Research output: Contribution to journalArticle

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