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Abstract #21351 Published in IGR 10-2
Endothelin-1 mediated regulation of extracellular matrix collagens in cells of human lamina cribrosa
Rao VR; Krishnamoorthy RR; Yorio TExperimental Eye Research 2008; 86: 886-894
See also comment(s) by George Cioffi •
Endothelin-1 (ET-1), a potent vaso-active peptide, mediates extracellular matrix regulation resulting in an increase in collagen deposition in various cell types and tissues and has been proposed to play a key role in glaucoma pathology. The role of ET-1 in the regulation of extracellular matrix collagens at the level of optic nerve head is not known. In this study we have examined the role of ET-1 in extracellular matrix collagen regulation in primary cultures of human lamina cribrosa cells. Our hypothesis is that ET-1 increases remodeling of the ECM of cells of the lamina cribrosa. Such actions could contribute to the development of optic neuropathy. QPCR analysis revealed that ET-1 mediated an increase in mRNA levels of collagen type I α1 and collagen type VI α1 chains at all doses of ET-1 with a significant increase at 1nM and 10nM concentration in LC cells. A dose-dependent increase in collagen type I and type VI protein deposition and secretion was also observed by Western blot in response to ET-1 and was significant at 10nM and 100nM concentrations of ET-1. ET-1 increased the [3H] proline uptake in LC cells suggesting that ET-1 contributed to an increase in total collagen synthesis in LC cells. ET-1-mediated increase in collagen type I, type VI and total collagen synthesis was significantly blocked by the ETA receptor antagonist, BQ610, as well as with the ETB) receptor antagonist, BQ788, suggesting the involvement of both receptor subtypes in ET-1 mediated collagen synthesis in LC cells. These results suggest that ET-1 regulates extracellular matrix collagen synthesis in LC cells and may contribute to ECM remodeling at the level of LC of POAG subjects who have elevated plasma and aqueous humor levels of endothelin-1.
Dr. V.R. Rao, Department of Pharmacology and Neuroscience, University of North Texas Health Science Center, 3500 Camp Bowie Boulevard, Fort Worth, TX 76107, USA
Classification:
2.14 Optic disc (Part of: 2 Anatomical structures in glaucoma)
2.3 Sclera (Part of: 2 Anatomical structures in glaucoma)
3.5 Molecular biology incl. SiRNA (Part of: 3 Laboratory methods)
