Galardin inhibits collagen degradation by rabbit keratocytes by inhibiting the activation of pro-matrix metalloproteinases - PubMed (original) (raw)
Galardin inhibits collagen degradation by rabbit keratocytes by inhibiting the activation of pro-matrix metalloproteinases
J L Hao et al. Exp Eye Res. 1999 May.
Abstract
We investigated the inhibitory action of a synthetic peptidyl hydroxamate inhibitor of matrix metalloproteinase (MMP), Galardin (GM6001), on collagen degradation by rabbit corneal stromal fibroblasts (keratocytes) cultured three-dimensionally in the type I collagen gel with medium containing interleukin 1alpha (IL-1alpha) and/or plasminogen. Degradation of collagen fibrils during culture was measured by the release of hydroxyproline, and activation of MMPs was also analyzed by gelatin zymography and Western blotting. Plasmin activity was measured using a synthetic substrate. In the absence of plasminogen, treatment of the cells with IL-1alpha in collagen gel greatly enhanced the production of proMMP-1, -3 and -9, but no significant degradation of collagen was detected. In the presence of plasminogen, IL-1alpha stimulated collagen degradation by keratocytes in a dose-dependent manner. This resulted from the plasminogen activator-plasmin system-dependent activation of proMMP-1, -3 and -9. Galardin inhibited the collagen degradation in a dose-dependent fashion in the presence of plasminogen, whether IL-1alpha was present or not. Galardin inhibited the activation of proMMP-3, and also prevented the activation of proMMP-9 and the conversion of MMP-1 intermediates to the fully active MMP-1. Galardin did not affect plasmin activity. The present results suggest that Galardin inhibits IL-1alpha-stimulated collagen degradation in the presence of plasminogen, resulting from not only inhibiting active MMPs but also preventing the conversion of proMMPs to active MMPs.
Copyright 1999 Academic Press.
Similar articles
- Effect of galardin on collagen degradation by Pseudomonas aeruginosa.
Hao JL, Nagano T, Nakamura M, Kumagai N, Mishima H, Nishida T. Hao JL, et al. Exp Eye Res. 1999 Dec;69(6):595-601. doi: 10.1006/exer.1999.0755. Exp Eye Res. 1999. PMID: 10620388 - Esculetin (dihydroxycoumarin) inhibits the production of matrix metalloproteinases in cartilage explants, and oral administration of its prodrug, CPA-926, suppresses cartilage destruction in rabbit experimental osteoarthritis.
Yamada H, Watanabe K, Saito T, Hayashi H, Niitani Y, Kikuchi T, Ito A, Fujikawa K, Lohmander LS. Yamada H, et al. J Rheumatol. 1999 Mar;26(3):654-62. J Rheumatol. 1999. PMID: 10090178 - Role of nuclear factor-kappaB in interleukin-1-induced collagen degradation by corneal fibroblasts.
Lu Y, Fukuda K, Li Q, Kumagai N, Nishida T. Lu Y, et al. Exp Eye Res. 2006 Sep;83(3):560-8. doi: 10.1016/j.exer.2006.02.008. Epub 2006 May 8. Exp Eye Res. 2006. PMID: 16684522 - Regulatory Mechanism of Collagen Degradation by Keratocytes and Corneal Inflammation: The Role of Urokinase-Type Plasminogen Activator.
Sugioka K, Mishima H, Kodama A, Itahashi M, Fukuda M, Shimomura Y. Sugioka K, et al. Cornea. 2016 Nov;35 Suppl 1:S59-S64. doi: 10.1097/ICO.0000000000000995. Cornea. 2016. PMID: 27661072 Review. - Pivotal Role of Corneal Fibroblasts in Progression to Corneal Ulcer in Bacterial Keratitis.
Nishida T, Sugioka K, Fukuda K, Murakami J. Nishida T, et al. Int J Mol Sci. 2021 Aug 20;22(16):8979. doi: 10.3390/ijms22168979. Int J Mol Sci. 2021. PMID: 34445684 Free PMC article. Review.
Cited by
- Combination therapy for ischemic stroke: Novel approaches to lengthen therapeutic window of tissue plasminogen activator.
Knecht T, Borlongan C, Dela Peña I. Knecht T, et al. Brain Circ. 2018 Jul-Sep;4(3):99-108. doi: 10.4103/bc.bc_21_18. Epub 2018 Oct 9. Brain Circ. 2018. PMID: 30450415 Free PMC article. Review. - MMP regulation of corneal keratocyte motility and mechanics in 3-D collagen matrices.
Zhou C, Petroll WM. Zhou C, et al. Exp Eye Res. 2014 Apr;121:147-60. doi: 10.1016/j.exer.2014.02.002. Epub 2014 Feb 14. Exp Eye Res. 2014. PMID: 24530619 Free PMC article. - Visualizing the Distribution of Matrix Metalloproteinases in Ischemic Brain Using In Vivo 19F-Magnetic Resonance Spectroscopic Imaging.
Huber VJ, Igarashi H, Ueki S, Terumitsu-Tsujita M, Nito C, Ohno K, Suzuki Y, Itoh K, Kwee IL, Nakada T. Huber VJ, et al. Contrast Media Mol Imaging. 2019 Jan 6;2019:8908943. doi: 10.1155/2019/8908943. eCollection 2019. Contrast Media Mol Imaging. 2019. PMID: 30723388 Free PMC article. - Effect of bioactive glass-containing dentin adhesives on microshear bond strength of composite restorations.
Mousavinasab SM, Sarandi F, Rezvanian P, Atai M, Mousavinasab S. Mousavinasab SM, et al. Dent Res J (Isfahan). 2023 Aug 28;20:95. eCollection 2023. Dent Res J (Isfahan). 2023. PMID: 37810451 Free PMC article. - Adjunctive Therapy Approaches for Ischemic Stroke: Innovations to Expand Time Window of Treatment.
Knecht T, Story J, Liu J, Davis W, Borlongan CV, Dela Peña IC. Knecht T, et al. Int J Mol Sci. 2017 Dec 19;18(12):2756. doi: 10.3390/ijms18122756. Int J Mol Sci. 2017. PMID: 29257093 Free PMC article. Review.
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Other Literature Sources