Effect of Cytoglobin Overexpression on Extracellular Matrix Component Synthesis in Human Tenon Fibroblasts

Overview

Journal Biol Res

Specialty Biology

Date 2019 Apr 18

PMID 30992080

Citations 6

Authors

Haiying Wei

Lili Lin

Xiaomei Zhang

Zhuolei Feng

Yeqing Wang

Yan You

Xiaodan Wang

Yongsheng Hou

Affiliations

Soon will be listed here.

Abstract

Background: Conjunctival filtering bleb scar formation is the main reason for the failure of glaucoma filtration surgery. Cytoglobin (Cygb) has been reported to play an important role in extracellular matrix (ECM) remodeling, fibrosis and tissue damage repairing. This study aimed to investigate the role of Cygb in anti-scarring during excessive conjunctival wound healing after glaucoma filtration surgery.

Methods: Cygb was overexpressed in human tenon fibroblasts (hTFs) by transfecting hTFs with lentiviral particles encoding pLenti6.2-FLAG-Cygb. Changes in the mRNA and protein levels of fibronectin, collagen I, collagen III, TGF-β1, and HIF1α were determined by RT-PCR and western blotting respectively.

Results: After Cygb overexpression, hTFs displayed no significant changes in visual appearance and cell counts compared to controls. Whereas, Cygb overexpression significantly decreased the mRNA and protein expression levels of collagen I, collagen III and fibronectin compared with control (p < 0.01). There was also a statistically significant decrease in the mRNA and protein levels of TGF-β1 and HIF-1α in hTFs with overexpressed Cygb compared with control group (p < 0.05).

Conclusion: Our study provided evidence that overexpression of Cygb decreased the expression levels of fibronectin, collagen I, collagen III, TGF-β1 and HIF-1α in hTFs. Therefore, therapies targeting Cygb expression in hTFs may pave a new way for clinicians to solve the problem of post-glaucoma surgery scarring.

Citing Articles

Sulforaphane inhibits TGF-β-induced fibrogenesis and inflammation in human Tenon's fibroblasts.

Liu Y, Huang Y, Guo Z, Yang C, Li Y, Li B Mol Vis. 2024; 30:200-210.

PMID: 39563680 PMC: 11575843.

AHCC inhibited hepatic stellate cells activation by regulation of cytoglobin induction via TLR2-SAPK/JNK pathway and collagen production via TLR4-NF-κβ pathway.

Urushima H, Matsubara T, Qiongya G, Daikoku A, Takayama M, Kadono C Am J Physiol Gastrointest Liver Physiol. 2024; 327(6):G741-G753.

PMID: 39316687 PMC: 11684891. DOI: 10.1152/ajpgi.00134.2024.

E3 ubiquitin ligase MARCH1 reduces inflammation and pyroptosis in cerebral ischemia-reperfusion injury via PCSK9 downregulation.

Guo H, Li W, Yang Z, Xing X Mamm Genome. 2024; 35(3):346-361.

PMID: 39115562 DOI: 10.1007/s00335-024-10055-2.

Sulforaphane inhibits TGF-β-induced fibrogenesis and inflammation in human Tenon's fibroblasts.

Liu Y, Huang Y, Guo Z, Yang C, Li Y, Li B Mol Vis. 2024; 29:306-316.

PMID: 38264611 PMC: 10805336.

Effectiveness of conjunctival bleb scarring by knock-down of heat shock protein 47 in rat model.

Wang W, Li H, Yan H Int J Ophthalmol. 2023; 16(10):1589-1594.

PMID: 37854383 PMC: 10559040. DOI: 10.18240/ijo.2023.10.05.

References

Chang L, Crowston J, Cordeiro M, Akbar A, Khaw P . The role of the immune system in conjunctival wound healing after glaucoma surgery. Surv Ophthalmol. 2000; 45(1):49-68. DOI: 10.1016/s0039-6257(00)00135-1. View

Kawada N, Kristensen D, Asahina K, Nakatani K, Minamiyama Y, Seki S . Characterization of a stellate cell activation-associated protein (STAP) with peroxidase activity found in rat hepatic stellate cells. J Biol Chem. 2001; 276(27):25318-23. DOI: 10.1074/jbc.M102630200. View

Trent 3rd J, Hargrove M . A ubiquitously expressed human hexacoordinate hemoglobin. J Biol Chem. 2002; 277(22):19538-45. DOI: 10.1074/jbc.M201934200. View

Nakatani K, Okuyama H, Shimahara Y, Saeki S, Kim D, Nakajima Y . Cytoglobin/STAP, its unique localization in splanchnic fibroblast-like cells and function in organ fibrogenesis. Lab Invest. 2003; 84(1):91-101. DOI: 10.1038/labinvest.3700013. View

Flogel U, Godecke A, Klotz L, Schrader J . Role of myoglobin in the antioxidant defense of the heart. FASEB J. 2004; 18(10):1156-8. DOI: 10.1096/fj.03-1382fje. View

Kirito K, Fox N, Komatsu N, Kaushansky K . Thrombopoietin enhances expression of vascular endothelial growth factor (VEGF) in primitive hematopoietic cells through induction of HIF-1alpha. Blood. 2005; 105(11):4258-63. PMC: 1895043. DOI: 10.1182/blood-2004-07-2712. View

Ostojic J, Sakaguchi D, de Lathouder Y, Hargrove M, Trent 3rd J, Kwon Y . Neuroglobin and cytoglobin: oxygen-binding proteins in retinal neurons. Invest Ophthalmol Vis Sci. 2006; 47(3):1016-23. DOI: 10.1167/iovs.05-0465. View

Xu R, Harrison P, Chen M, Li L, Tsui T, Fung P . Cytoglobin overexpression protects against damage-induced fibrosis. Mol Ther. 2006; 13(6):1093-100. DOI: 10.1016/j.ymthe.2005.11.027. View

Saika S, Yamanaka O, Sumioka T, Miyamoto T, Miyazaki K, Okada Y . Fibrotic disorders in the eye: targets of gene therapy. Prog Retin Eye Res. 2008; 27(2):177-96. DOI: 10.1016/j.preteyeres.2007.12.002. View

10.

Gurtner G, Werner S, Barrandon Y, Longaker M . Wound repair and regeneration. Nature. 2008; 453(7193):314-21. DOI: 10.1038/nature07039. View

11.

Ostojic J, Grozdanic S, Syed N, Hargrove M, Trent 3rd J, Kuehn M . Neuroglobin and cytoglobin distribution in the anterior eye segment: a comparative immunohistochemical study. J Histochem Cytochem. 2008; 56(9):863-72. PMC: 2516955. DOI: 10.1369/jhc.2008.951392. View

12.

Georgoulas S, Dahlmann-Noor A, Brocchini S, Khaw P . Modulation of wound healing during and after glaucoma surgery. Prog Brain Res. 2008; 173:237-54. DOI: 10.1016/S0079-6123(08)01117-5. View

13.

Man K, Philipsen S, Tan-Un K . Localization and expression pattern of cytoglobin in carbon tetrachloride-induced liver fibrosis. Toxicol Lett. 2008; 183(1-3):36-44. DOI: 10.1016/j.toxlet.2008.09.015. View

14.

Bao P, Kodra A, Tomic-Canic M, Golinko M, Ehrlich H, Brem H . The role of vascular endothelial growth factor in wound healing. J Surg Res. 2008; 153(2):347-58. PMC: 2728016. DOI: 10.1016/j.jss.2008.04.023. View

15.

How A, Chua J, Charlton A, Su R, Lim M, Kumar R . Combined treatment with bevacizumab and 5-fluorouracil attenuates the postoperative scarring response after experimental glaucoma filtration surgery. Invest Ophthalmol Vis Sci. 2009; 51(2):928-32. DOI: 10.1167/iovs.09-3949. View

16.

Emara M, Turner A, Allalunis-Turner J . Hypoxic regulation of cytoglobin and neuroglobin expression in human normal and tumor tissues. Cancer Cell Int. 2010; 10:33. PMC: 2945342. DOI: 10.1186/1475-2867-10-33. View

17.

Nishi H, Inagi R, Kawada N, Yoshizato K, Mimura I, Fujita T . Cytoglobin, a novel member of the globin family, protects kidney fibroblasts against oxidative stress under ischemic conditions. Am J Pathol. 2011; 178(1):128-39. PMC: 3069879. DOI: 10.1016/j.ajpath.2010.11.011. View

18.

Nurden A . Platelets, inflammation and tissue regeneration. Thromb Haemost. 2011; 105 Suppl 1:S13-33. DOI: 10.1160/THS10-11-0720. View

19.

Thuy L, Morita T, Yoshida K, Wakasa K, Iizuka M, Ogawa T . Promotion of liver and lung tumorigenesis in DEN-treated cytoglobin-deficient mice. Am J Pathol. 2011; 179(2):1050-60. PMC: 3157247. DOI: 10.1016/j.ajpath.2011.05.006. View

20.

Gedde S, Singh K, Schiffman J, Feuer W . The Tube Versus Trabeculectomy Study: interpretation of results and application to clinical practice. Curr Opin Ophthalmol. 2012; 23(2):118-26. DOI: 10.1097/ICU.0b013e32834ff2d1. View