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targeting non-muscle myosin ii promotes corneal endothelial migration through regulating lamellipodial dynamics
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نویسنده
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ho wei-ting ,chang jung-shen ,chou san-fang ,hwang wei-lun ,shih po-jen ,chang shu-wen ,yang muh-hwa ,jou tzuu-shuh ,wang i-jong
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منبع
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journal of molecular medicine - 2019 - دوره : 97 - شماره : 9 - صفحه:1345 -1357
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چکیده
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Corneal endothelial cell (cec) dysfunction causes corneal edema that lead to blindness. in addition to corneal transplantation, simple descemetorhexis has been proposed to treat centrally located disease with adequate peripheral cell reserve, but promoting the centripetal migration of cecs is pivotal to this strategy. here, we show that targeting non-muscle myosin ii (nmii) activity by y27632, a rock inhibitor, or blebbistatin, a selective nmii inhibitor, promotes directional migration of cecs and accelerates in vitro wound healing. the lamellipodial protrusion persistence is increased, and actin retrograde flow is decreased after nmii inhibition. counteracting lamellipodial protrusion by actin-related protein 2/3 (arp2/3) inhibitor abolishes this migration-promoting effect. although both y27632 and blebbistatin accelerate wound healing, cell junctional integrity and barrier function are better preserved after blebbistatin treatment, leading to more rapid corneal deturgescence in rabbit corneal endothelial wounding model. our findings indicate that nmii is a promising therapeutic target in the treatment of cec dysfunction.
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کلیدواژه
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corneal endothelial cell ,non-muscle myosin ii ,cell migration ,wound healing ,lamellipodia
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آدرس
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far eastern memorial hospital, department of ophthalmology, taiwan. national taiwan university, graduate institute of clinical medicine, college of medicine, taiwan, national taiwan university hospital, department of ophthalmology, taiwan, far eastern memorial hospital, department of medical research, taiwan, national yang‐ming university, department of biotechnology and laboratory science in medicine, taiwan, national university of kaohsiung, department of civil and environmental engineering, taiwan, far eastern memorial hospital, department of ophthalmology, taiwan. national taiwan university, college of medicine, taiwan, national yang-ming university, institute of clinical medicine, taiwan. taipei veterans general hospital, division of medical oncology, department of oncology, taiwan, national taiwan university, graduate institute of clinical medicine, college of medicine, center of precision medicine, college of medicine, taiwan, national taiwan university hospital, department of ophthalmology, taiwan. national taiwan university, college of medicine, taiwan
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Authors
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