Abstract
• Purpose: To investigate the effect of fibrostatin C, a prolyl 4-hydroxylase (PH) inhibitor produced byStreptomyces catenutae subsp. griseospora, on type I collagen secretion by human Tenon's capsule fibroblasts (TCFs) in vitro, as an indication of the potential therapeutic efficacy of this compound in antifibrotic therapy after glaucoma filtering surgery. • Methods: The concentrations of type II procollagen COOH-terminal peptide (PIP) in culture medium or cell lysate were determined by immunoassays. For comparison with its effect on PIP secretion, we determined the effects of the agent on the secretion of other peptides, including laminin, vitronectin receptor, and a metalloproteinase inhibitor. The expression of collagens I and 111, fibronectin, and PH by TCFs was examined by immunohistochemistry, and cellular ultrastructure was evaluated by transmission electron microscopy. • Results: Fibrostatin C (50 μM) significantly reduced the concentration of PIP in culture medium and increased its concentration in the cell lysate in a dose-dependent manner, but it had no effect on the secretion of other peptides. Cell viability and proliferation were not affected by fibrostatin C. Fibrostatin C also increased the number of cytoplasmic granules immunoreactive with antibodies to collagen I or III, but had no effect on fibronectin or PH immunoreactivity. Ultrastructurally, cisternae of the endoplasmic reticulum were dilated in fibrostatin C-treated TCFs, consistent with the retention of underhydroxylated collagen precursors in this organelle. • Conclusions: Fibrostatin C inhibits the secretion of type I collagen by cultured TCFs. This agent may thus prove therapeutically beneficial for inhibiting the excess fibrosis in the wound of filtering surgery.
Similar content being viewed by others
References
Addicks EM, Quigley HA, Green WR, Robin AL (1983) Histologic characteristics of filtering blebs in glaucomatous eyes. Arch Ophthalmol 101:795–798
Bai Y, Muragaki Y, Obata K, Iwata K, Ooshima A (1986) Immunological properties of monoclonal antibodies to human and rat prolyl 4-hydroxylase. J Biochem 99:1563–1570
Berg RA, Schwartz ML, Crystal RG (1980) Regulation of the production of secretory proteins: intracellular degradation of newly synthesized “defective” collagen. Proc Natl Acad Sci USA 77:4746–4750
Berg RA, Schwartz ML, Rome LH, Crystal RG (1984) Lysosomal function in the degradation of defective collagen in cultured lung fibroblasts. Biochemistry 23:2134–2138
Cheng SY, Gong QH, Parkinson C, Robinson EA, Appella E, Merlino GT, Pasten I (1987) The nucleotide sequence of a human cellular thyroid hormone binding protein present in endoplasmic reticulum. J Biol Chem 262:11221–11227
De Clerck YA, Yean RD, Ratzkin BJ, Lu HS, Langley KE (1989) Purification and characterization of two related but distinct metalloproteinase inhibitors secreted by bovine aortic endothelial cells. J Biol Chem 264:17445–17453
Desjardins DC, Parrish RK II, Folberg R, Nevarez J, Heuer DK, Gressel MG (1986) Wound healing after filtering surgery in owl monkeys. Arch Ophthalmol 104:1835–1839
Eriksen EF, Charles P, Melsen F, Mosekilde L, Risteli L, Listeli J (1993) Serum markers of type I collagen formation and degradation in metabolic bone disease: correlation with bone histomorphometry. J Bone Miner Res 8:127–132
Gressel MG, Parrish RK II, Folberg R (1984) 5-Fluorouracil and glaucoma filtering surgery. I. An animal model. Ophthalmology 91:378–383
Handa JT, Murad S, Jaffe GJ (1993) Minoxidil inhibits ocular cell proliferation and lysyl hydroxylase activity. Invest Ophthalmol Vis Sci 34:567–575
Hata R, Senoo H (1989)l-Ascorbic acid 2-phosphate stimulates collagen accumulation, cell proliferation, and formation of a three-dimensional tissue-like substance by skin fibroblasts. J Cell Physiol 138:8–16
Helaakoski T, Vouri K, Myllyla R, Kivirikko KI, Pihlajaniemi T (1989) Molecular cloning of the α-subunit of human prolyl 4-hydroxylase: the complete cDNA-derived amino acid sequence and evidence for alternative splicing of RNA transcripts. Proc Natl Acad Sci USA 86:4392–4396
Heuer DK, Gressel MG, Parrish RK II, Folberg R, Dillberger JE, Altman NH (1986) Topical fluorouracil. Postoperative administration in an animal model of glaucoma filtering surgery. Arch Ophthalmol 104:132–136
Heuer DK, Parrish RK II, Gressel MG, Hodapp E, Palmberg PF, Anderson DR (1986) 5-Fluorouracil and glaucoma filtering surgery. 111. Intermediate follow-up of a pilot study. Ophthalmology 93:1537–1546
Ishimaru T, Kanamaru T, Ohta K, Okazaki H (1987) Fibrostatins, new inhibitors of prolyl hydroxylase. 1. Taxonomy, isolations and characterization. J Antibiotics 40:1231–1238
Ishimaru T, Kanamaru T, Takahashi T, Okazaki H (1988) Inhibition of prolyl hydroxylase activity and collagen biosynthesis by fibrostatin C, a novel inhibitor produced byStreptomyces catenulae subsp.griseospora No 23924. J Antibiotics 41:1668–1674
Jampel HD (1992) Effect of brief exposure to mitomycin C on viability and proliferation of human Tenon's capsule fibroblasts. Ophthalmology 99:1471–1476
Jampel HD, McGuigan LJB, Dunkelberger GR, L'Hernault NL, Quigley HA (1988) Cellular proliferation after experimental glaucoma filteration surgery. Arch Ophthalmol 106:89–94
Jampel HD, Pasquale LR, Dibernardo C (1992) Hypotony maculopathy following trabeculectomy with mitomycin C. Arch Opthalmol 110:1049–1050
Kawaguchi Y, Harigai M, Kitani A, Suzuki K, Kawakami M, Ishizuka T, Hara M, Kawagoe M, Nakamura H (1992) Effect of prolyl 4-hydroxylase inhibitor on fibroblast collagen production in vitro: an approach to the treatment of systemic sclerosis. J Rheumtol 19:1710–1715
Kitazawa Y, Kawase K, Matsushita H, Minobe M (1991) Trabeculectomy with mitomycin. A comparative study with fluorouracil. Arch Ophthalmol 109:1693–1698
Kivirikko KI, Myllyla R (1985) Posttranslational processing of procollagens. Ann NY Acad Sci 460:187–201
Kivirikko KI, Myllyla R, Pihlajaniemi T (1989) Protein hydroxylation: prolyl 4-hydroxylase, an enzyme with four cosubstrates and a multifunctional subunit. FASEB J 3:1609–1617
Knapp A, Heuer DK, Stern GA, Driebe WT (1987) Serious corneal complications of glaucoma filtering surgery with postoperative 5-fluorouracil. Am J Ophthalmol 103:183–187
Kodama S, Iwata K, Iwata H, Yamashita K, Hayakawa T (1990) Rapid one-step sandwich enzyme immunoassay for tissue inhibitor of metalloproteinases. An application for rheumatoid arthritis serum and plasma. J Immunol Method 127:103–108
Koivu J, Myllyla R, Helaakoski T, Pihlajaniemi T, Tasanen K, Kivirikko KI (1987) A single polypeptide acts both as the β-subunit of prolyl 4-hydroxylase and as a protein disulfideisomerase. J Biol Chem 262:6447–6449
Lee DA, Lee TC, Cortes AE, Kitada S (1990) Effects of mithramycin, mitomycin, daunorubicin and bleomycin on human subconjunctival fibroblast attachment and proliferation. Invest Ophthalmol Vis Sci 31:2136–2144
Lee DA, Shapourifar-Tehrani S, Kitada S (1990) The effect of 5-fluorouracil and cytarabine on human fibroblasts from Tenon's capsule. Invest Ophthalmol Vis Sci 31:1848–1855
Liotta LA, Vembu D, Kleinmann HK, Martin GR, Boone C (1987) Collagen required for proliferation of cultured connective tissue cells but not their transformed counterparts. Nature 272:622–624
Low SQ, Kitada S, Lee DA (1991) Interferon-γ inhibits collagen synthesis by human Tenon's capsule fibroblasts in vitro. Invest Ophthalmol Vis Sci 32:2964–2969
McGuigan LJB, Mason RP, Sanchez R, Quigley HA (1987)d-Penicillamine and beta-aminopropionitrile effects on experimental filtering surgery. Invest Ophthalmol Vis Sci 28:1625–1629
Melkko J, Niemi S, Risteli L, Risteli J (1990) Radioimmunoassay of the carboxyterminal propeptide of human type I procollagen. Clin Chem 35:1328–1332
Murad S, Pinnell SR (1987) Suppression of fibroblast proliferation and lysyl hydroxylase activity by minoxidil. J Biol Chem 262:11973–11978
Mussini E, Hutton JJ Jr, Udenfriend S (1967) Collagen proline hydroxylase in wound healing, granuloma formation, scurvy, and growth. Science 157:927–929
Nguyen KD, Hoang AT, Lee DA (1994) Transcriptional control of human Tenon's capsule fibroblast collagen synthesis in vitro by gamma-interferon. Invest Ophthalmol Vis Sci 35:3064–3070
Nomura H, Ishiguro T, Morimoto S (1969) Studies onl-ascorbic acid derivatives. 111. Bis (l-ascorbic acid3,3′) phosphate andl-ascorbic acid 2-phosphate. Chem Pharm Bull (Tokyo) 17:387–393
Ohta K, Kasahara F, Ishimura T, Wada Y, Kanamaru T, Okazaki H (1987) Structures of fibrostatins, new inhibitors of prolyl hydroxylase. J Antibiotics 40:1239–1248
Olsen BR, Berg RA, Kishida Y, Prockop DJ (1973) Collagen synthesis. Localization of prolyl hydroxylase in tendon cells detected with ferritin-labeled antibody. Science 182:825–827
Ooshima A, Fuller GC, Cardinale GJ, Spector S, Udenfriend S (1974) Increased collagen synthesis in blood vessels of hypertensive rats and its reversal by antihypertensive agents. Proc Natl Acad Sci USA 71:3019–3023
Ooshima A, Fuller GC, Cardinale GJ, Spector S, Udenfriend S (1975) Collagen biosynthesis in blood vessels of brain and other tissues of the hypertensive rat. Science 190:898–900
Parfitt AM, Simon LS, Villanueva AR, Krane SM (1987) Procollagen type I carboxy-terminal extension peptide in serum as a marker of collagen biosynthesis in bone. Correlation with iliac bone formation rates and comparison with total alkaline phosphatase. J Bone Miner Res 2:427–436
Pasquale LIZ, Thibault D, Dorman-Pease ML, Quigley HA, Jampel HD (1992) Effect of topical mitomycin C on glaucoma filteration surgery in monkeys. Ophthalmology 99:14–18
Pihlajaniemi T, Helaakoski T, Tasanen K, Myllyle R, Huhtala ML, Koivu J, Kivirikko KI (1987) Molecular cloning of the β-subunit of human prolyl 4-hydroxylase. This subunit and protein disulfide isomerase are products of the same gene. EMBO J 6:643–649
Pihlajaniemi T, Myllyla R, Kivirikko KI (1991) Prolyl 4-hydroxylase and its role in collagen synthesis. J Hepatol 13 [Suppl 3]:S2-S7
Preissner KT, Denne J (1991) Structure and biological role of vitronectin. Ann Rev Cell Biol 7:275–310
Saika S, Kanagawa R, Uenoyama K, Hiroi K, Hiraoka J (1991)l-Ascorbic acid 2-phosphate, a phosphate derivative ofl-ascorbic acid, enhances the growth of cultured rabbit keratocytes. Graefe's Arch Clin Exp Ophthalmol 229:79–83
Saika S, Uenoyama K, Hiroi K, Ooshima A (1992)l-Ascorbic acid 2-phosphate enhances the production of type I and type III collagen peptides in cultured rabbit keratocytes. Ophthalmic Res 24:68–72
Saika S, Ooshima A, Hashizume N, Yamanaka O, Tanaka S, Okada Y, Kobata S (1995) Effect of a lysyl hydroxylase inhibitor, minoxidil, on ultrastructure and behavior of cultured rabbit subconjunctival fibrobasts. Graefe's Arch Clin Exp Ophthalmol 233:347–353
Sasaki T, Holeyfield KC, Uitto J (1987) Doxorubicin-induced inhibition of prolyl hydroxylation during collagen biosynthesis in human skin fibroblast culture. J Clin Invest 80:1735–1741
Sasaki T, Majamaa K, Uitto J (1987) Reduction of collagen production in keloid fibroblast cultures by ethyl-3,4-dihydroxybenzoate. J Biol Chem 262:9397–9403
Shapiro MS, Thoft RA, Friend J, Parrish RK II, Gressel MG (1985) 5-Fluorouracil toxicity to the ocular surface epithelium. Invest Ophthalmol Vis Sci 26:580–583
Takeuchi T, Kivirikko KI, Prockop DJ (1967) Increased protocollagen hydroxylase activity in the liver of rats with hepatic fibrosis. Biochem Biophys Res Commun 28:940–944
Tan EML, Ryhanen L, Uitto J (1983) Proline analogs inhibit skin fibroblast growth and collagen production in culture. J Invest Dermatol 80:261–267
Tang S-S, Trachman PC, Kagan HM (1983) Reaction of aortic lysyl oxidase with β-aminopropionitrile. J Biol Chem 258:4331–4338
Ticho U, Ophir A (1993) Late complications after glaucoma filtering surgery with adjunctive 5-fluorouracil. Am J Ophthalmol 115:506–510
Tuderman L, Prockop DJ (1982) N-Proteinase: properties of the enzyme purified from chick embryo tendons. Eur J Biochem 125:545–549
Yamamoto T, Varani J, Soong HJ, Lichter PR (1990) Effects of 5-fluorouracil and mitomycin C on cultured rabbit subconjunctival fibroblasts. Ophthalmology 97:1204–1210
Yamanaka O, Saika S, Ooshima A (1995) Gamma-interferon effects on human Tenon's capsule fibroblasts in vitro. Invest Ophthalmol Vis Sci [Suppl] 35:91 (ARVO abstract)
Yeowell HN, Ha V, Walker LC, Murad S, Pinnell SR (1992) Characterization of a partial cDNA for lysyl hydroxylase from human skin fibroblasts; lysyl hydroxylase mRNAs are regulated differently by minoxidil derivatives and hydralazine. J Invest Dermatol 99:864–986
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Saika, S., Ooshima, A., Yamanaka, O. et al. Effect of fibrostatin C, an inhibitor of prolyl 4-hydroxylase, on collagen secretion by human Tenon's capsule fibroblasts in vitro. Graefe's Arch Clin Exp Ophthalmol 234 (Suppl 1), S214–S222 (1996). https://doi.org/10.1007/BF02343075
Received:
Revised:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF02343075