PURPOSE: The authors investigated the role of myosin light chain kinase (MYLK) and transforming growth factor beta (TGFbeta) receptor pathways in optic nerve head (ONH) astrocyte migration. They further investigated how the expression of these genes is altered by elevated hydrostatic pressure (HP). METHODS: PCR was used to determine the isoforms of MYLK expressed in ONH astrocytes. siRNAs against MYLK (all isoforms) and TGFbeta receptor 2 (TGFBR2) were prepared and tested for effects on the migration of cultured ONH astrocytes. Finally, the effects of elevated HP (24-96 hours) on the expression of MYLK isoforms and selected TGFbeta pathway components were measured. RESULTS: Multiple isoforms of MYLK are present in ONH astrocytes from Caucasian (CA) and African American (AA) donors. Both populations express the short form (MYLK-130) and the long form (MYLK-210) of MYLK and a splicing variant within MYLK-210. MYLK-directed siRNA decreased MYLK expression and cell migration compared with control siRNA. siRNA directed against TGFbeta receptor 2 also decreased cell migration compared with control and decreased extracellular matrix genes regulated by TGFbeta signaling. Elevated HP increased the expression of MYLK-130 and MYLK-210 in both populations of astrocytes. However, TGFbeta2 was uniquely upregulated by exposure to elevated HP in CA compared with AA astrocytes. CONCLUSIONS: Differential expression of TGFbeta pathway genes and MYLK isoforms observed in populations of glaucomatous astrocytes applies to the elevated HP model system. MYLK may be a new target for intervention in glaucoma to alter reactive astrocyte migration in the ONH.
PURPOSE: The authors investigated the role of myosin light chain kinase (MYLK) and transforming growth factor beta (TGFbeta) receptor pathways in optic nerve head (ONH) astrocyte migration. They further investigated how the expression of these genes is altered by elevated hydrostatic pressure (HP). METHODS: PCR was used to determine the isoforms of MYLK expressed in ONH astrocytes. siRNAs against MYLK (all isoforms) and TGFbeta receptor 2 (TGFBR2) were prepared and tested for effects on the migration of cultured ONH astrocytes. Finally, the effects of elevated HP (24-96 hours) on the expression of MYLK isoforms and selected TGFbeta pathway components were measured. RESULTS: Multiple isoforms of MYLK are present in ONH astrocytes from Caucasian (CA) and African American (AA) donors. Both populations express the short form (MYLK-130) and the long form (MYLK-210) of MYLK and a splicing variant within MYLK-210. MYLK-directed siRNA decreased MYLK expression and cell migration compared with control siRNA. siRNA directed against TGFbeta receptor 2 also decreased cell migration compared with control and decreased extracellular matrix genes regulated by TGFbeta signaling. Elevated HP increased the expression of MYLK-130 and MYLK-210 in both populations of astrocytes. However, TGFbeta2 was uniquely upregulated by exposure to elevated HP in CA compared with AA astrocytes. CONCLUSIONS: Differential expression of TGFbeta pathway genes and MYLK isoforms observed in populations of glaucomatous astrocytes applies to the elevated HP model system. MYLK may be a new target for intervention in glaucoma to alter reactive astrocyte migration in the ONH.
Authors: K G Birukov; J P Schavocky; V P Shirinsky; M V Chibalina; L J Van Eldik; D M Watterson Journal: J Cell Biochem Date: 1998-09-01 Impact factor: 4.429
Authors: Hiroshi Nakamura; Shahid S Siddiqui; Xiang Shen; Asrar B Malik; Jose S Pulido; Nalin M Kumar; Beatrice Y J T Yue Journal: Mol Vis Date: 2004-10-04 Impact factor: 2.367
Authors: Ian D Danford; Lana D Verkuil; Daniel J Choi; David W Collins; Harini V Gudiseva; Katherine E Uyhazi; Marisa K Lau; Levi N Kanu; Gregory R Grant; Venkata R M Chavali; Joan M O'Brien Journal: Prog Retin Eye Res Date: 2017-02-20 Impact factor: 21.198
Authors: Janey L Wiggs; Brian L Yaspan; Michael A Hauser; Jae H Kang; R Rand Allingham; Lana M Olson; Wael Abdrabou; Bao J Fan; Dan Y Wang; Wendy Brodeur; Donald L Budenz; Joseph Caprioli; Andrew Crenshaw; Kristy Crooks; Elizabeth Delbono; Kimberly F Doheny; David S Friedman; Douglas Gaasterland; Terry Gaasterland; Cathy Laurie; Richard K Lee; Paul R Lichter; Stephanie Loomis; Yutao Liu; Felipe A Medeiros; Cathy McCarty; Daniel Mirel; Sayoko E Moroi; David C Musch; Anthony Realini; Frank W Rozsa; Joel S Schuman; Kathleen Scott; Kuldev Singh; Joshua D Stein; Edward H Trager; Paul Vanveldhuisen; Douglas Vollrath; Gadi Wollstein; Sachiko Yoneyama; Kang Zhang; Robert N Weinreb; Jason Ernst; Manolis Kellis; Tomohiro Masuda; Don Zack; Julia E Richards; Margaret Pericak-Vance; Louis R Pasquale; Jonathan L Haines Journal: PLoS Genet Date: 2012-04-26 Impact factor: 5.917