Src mediates TGF-β-induced intraocular pressure elevation in glaucoma

Journal of Cellular Physiology
Teruhisa TsukamotoMasato Okada

Abstract

Glaucoma, a progressive and irreversible optic neuropathy, is one of the leading causes of vision impairment worldwide. Elevation of intraocular pressure (IOP) due to transforming growth factor-β (TGF-β)-induced dysfunction of the trabecular meshwork is a risk factor for glaucoma, but the underlying molecular mechanisms remain elusive. Here, we show that Src kinase is involved in TGF-β-induced IOP elevation. We observed that dasatinib, a potent Src inhibitor, suppressed TGF-β2-induced IOP in rat eyes. Mechanistic analyses in human trabecular meshwork cells showed that TGF-β2 activated Src signaling and concomitantly increased cytoskeletal remodeling, cell adhesion, and extracellular matrix (ECM) accumulation. Src was activated via TGF-β2-induced upregulation of the Src scaffolding protein CasL, which mediates the assembly of focal adhesions, cytoskeletal remodeling, and ECM deposition. Activation of Src suppressed the expression of tissue plasminogen activator, thereby attenuating ECM degradation. Furthermore, the Src inhibitor ameliorated TGF-β2-induced changes in the contractile and adhesive characteristics of trabecular meshwork cells, and ECM deposition. These findings underscore the crucial role of Src activity in TGF-β-in...Continue Reading

References

Jun 1, 1992·Korean Journal of Ophthalmology : KJO·K S KimI S Kim
Jan 1, 1987·Annual Review of Cell Biology·R Jove, H Hanafusa
Feb 1, 1989·Mechanisms of Ageing and Development·M A Babizhayev, M W Brodskaya
Jan 1, 1989·Experimental Eye Research·E Lütjen-DrecollJ Mollenhauer
Jun 7, 1996·Biochimica Et Biophysica Acta·M T Brown, J A Cooper
Jan 1, 1997·Annual Review of Cell and Developmental Biology·S M Thomas, J S Brugge
Apr 5, 2000·Progress in Retinal and Eye Research·M WiederholtF Stumpff
Oct 19, 2001·Oncogene·M D Schaller
Jun 14, 2002·Japanese Journal of Ophthalmology·Yuko Ochiai, Haruyuki Ochiai
Oct 9, 2002·Archives of Ophthalmology·Anders HeijlUNKNOWN Early Manifest Glaucoma Trial Group
Dec 24, 2003·Investigative Ophthalmology & Visual Science·Johannes GottankaC Ross Ethier
May 8, 2004·Trends in Cell Biology·Neil O Carragher, Margaret C Frame
Jun 2, 2004·Nature Reviews. Cancer·Timothy J Yeatman
Oct 19, 2004·Oncogene·Sarah J Parsons, J Thomas Parsons
Oct 19, 2004·Oncogene·Martin P Playford, Michael D Schaller
May 7, 2005·Eye·J P Kersey, D C Broadway
Sep 21, 2005·Journal of Vascular Surgery·Zhe YangHong Yu
Jan 3, 2006·Experimental Eye Research·Mark Johnson
Jun 28, 2006·Clinical Lung Cancer·David Lee, Oliver Gautschi
Jan 16, 2007·Experimental Eye Research·A Thomas ReadC Ross Ethier
Feb 24, 2007·Current Opinion in Cell Biology·Susumu Itoh, Peter ten Dijke
Feb 28, 2007·Investigative Ophthalmology & Visual Science·Robert J WordingerAbbot F Clark
Dec 1, 2007·Growth Factors·Kazuhito YonedaKei Tashiro
Apr 3, 2009·Journal of Cell Science·Stephan Huveneers, Erik H J Danen
Sep 10, 2009·Cancer Research·Eugene IzumchenkoErica A Golemis
Oct 20, 2009·Proceedings of the Japan Academy. Series B, Physical and Biological Sciences·Kohei Miyazono
Apr 2, 2011·Lancet·Harry A Quigley
Nov 10, 2012·International Journal of Biological Sciences·Masato Okada
Sep 5, 2013·Investigative Ophthalmology & Visual Science·Thomas WeckerGünther Schlunck
Nov 2, 2013·Investigative Ophthalmology & Visual Science·Rosana GeromettaJohn Danias
May 30, 2015·Investigative Ophthalmology & Visual Science·Uttio Roy ChowdhuryMichael P Fautsch

❮ Previous
Next ❯

Related Concepts

Related Feeds

Adhesion Molecules in Health and Disease

Cell adhesion molecules are a subset of cell adhesion proteins located on the cell surface involved in binding with other cells or with the extracellular matrix in the process called cell adhesion. In essence, cell adhesion molecules help cells stick to each other and to their surroundings. Cell adhesion is a crucial component in maintaining tissue structure and function. Discover the latest research on adhesion molecule and their role in health and disease here.

Related Papers

Experimental Eye Research
Jaclyn Y BermudezAbbot F Clark
Journal of Ocular Pharmacology and Therapeutics : the Official Journal of the Association for Ocular Pharmacology and Therapeutics
Robert J WordingerAbbot F Clark
© 2022 Meta ULC. All rights reserved