Presentation Title (IN ALL CAPS)

Endothelin-1 induced Fibronectin expression via c-Jun

Departmental Affiliation and City, State, Zip for All Authors

California State University, Northridge; Department of Pharmacology & Neuroscience, North Texas Eye Research Institute, UNTHSC; School of Pharmaceutical Science, UNTHSC

Scientific Abstract

Glaucoma is an optic disease that is characterized by slow neurodegeneration of the optical nerves and steady loss of retinal ganglion cells. Over 70 million people suffer from glaucoma and it is estimated that over 118 million will suffer from it in 2040. A prime factor causing glaucoma is an increased in intraocular pressure (IOP) but the mechanism in how IOP contributes to glaucoma is still being studied. Blocking the aqueous humor through trabecular meshwork(TM) is a major contributor for the IOP elevation. Endothelin (ET-1) is a potent vasoconstrictor playing an important role in vascular system. Previous research has discovered that ET-1 and its ETA/ETB receptors are also involved in the pathogenesis of glaucoma. The current study aims to test whether ET-1 induced fibronectin deposition at TM. We hypothesize that ET-1 induces overexpression of fibronectin through c-Jun-mediated signaling pathway. Primary human TM cells were pretreated with c-Jun siRNA, SP600125 (a JNK inhibitor to block activation of c-Jun) or ET receptor antagonist’s followed with ET-1 treatment. Protein levels of fibronectin and c-Jun were detected using immunoblotting. An increase of fibronectin and c-Jun were detected in TM cells treated with ET-1 for 24-72 hours. Fibronectin was increased as a result of c-Jun being partially terminated by the knockdown of c-Jun by C-Jun siRNA. Blocking of ETA/ETB by BQ610/BQ788 reduced the expression of fibronectin. Our results preliminarily demonstrate that ET-1 induces the expression of fibronectin through c-Jun mediated signaling pathway, suggesting that ET-1 may cause the accumulation of fibronectin at TM contributing to IOP elevation.

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Endothelin-1 induced Fibronectin expression via c-Jun

Glaucoma is an optic disease that is characterized by slow neurodegeneration of the optical nerves and steady loss of retinal ganglion cells. Over 70 million people suffer from glaucoma and it is estimated that over 118 million will suffer from it in 2040. A prime factor causing glaucoma is an increased in intraocular pressure (IOP) but the mechanism in how IOP contributes to glaucoma is still being studied. Blocking the aqueous humor through trabecular meshwork(TM) is a major contributor for the IOP elevation. Endothelin (ET-1) is a potent vasoconstrictor playing an important role in vascular system. Previous research has discovered that ET-1 and its ETA/ETB receptors are also involved in the pathogenesis of glaucoma. The current study aims to test whether ET-1 induced fibronectin deposition at TM. We hypothesize that ET-1 induces overexpression of fibronectin through c-Jun-mediated signaling pathway. Primary human TM cells were pretreated with c-Jun siRNA, SP600125 (a JNK inhibitor to block activation of c-Jun) or ET receptor antagonist’s followed with ET-1 treatment. Protein levels of fibronectin and c-Jun were detected using immunoblotting. An increase of fibronectin and c-Jun were detected in TM cells treated with ET-1 for 24-72 hours. Fibronectin was increased as a result of c-Jun being partially terminated by the knockdown of c-Jun by C-Jun siRNA. Blocking of ETA/ETB by BQ610/BQ788 reduced the expression of fibronectin. Our results preliminarily demonstrate that ET-1 induces the expression of fibronectin through c-Jun mediated signaling pathway, suggesting that ET-1 may cause the accumulation of fibronectin at TM contributing to IOP elevation.

Manuscript Number

1056