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Hic-5 Regulates Actin Cytoskeletal Reorganization and Expression of Fibrogenic Markers and Myocilin in Trabecular Meshwork Cells.

Publication ,  Journal Article
Pattabiraman, PP; Rao, PV
Published in: Invest Ophthalmol Vis Sci
August 2015

PURPOSE: To explore the role of inducible focal adhesion (FA) protein Hic-5 in actin cytoskeletal reorganization, FA formation, fibrogenic activity, and expression of myocilin in trabecular meshwork (TM) cells. METHODS: Using primary cultures of human TM (HTM) cells, the effects of various external factors on Hic-5 protein levels, as well as the effects of recombinant Hic-5 and Hic-5 small interfering RNA (siRNA) on actin cytoskeleton, FAs, myocilin, α-smooth muscle actin (αSMA), and collagen-1 were determined by immunofluorescence and immunoblot analyses. RESULTS: Hic-5 distributes discretely to the FAs in HTM cells and throughout the TM and Schlemm's canal of the human aqueous humor (AH) outflow pathway. Transforming growth factor-β2 (TGF-β2), endothelin-1, lysophosphatidic acid, hydrogen peroxide, and RhoA significantly increased Hic-5 protein levels in HTM cells in association with reorganization of actin cytoskeleton and FAs. While recombinant Hic-5 induced actin stress fibers, FAs, αv integrin redistribution to the FAs, increased levels of αSMA, collagen-1, and myocilin, Hic-5 siRNA suppressed most of these responses in HTM cells. Hic-5 siRNA also suppressed TGF-β2-induced fibrogenic activity and dexamethasone-induced myocilin expression in HTM cells. CONCLUSIONS: Taken together, these results reveal that Hic-5, whose levels were increased by various external factors implicated in elevated intraocular pressure, induces actin cytoskeletal reorganization, FAs, expression of fibrogenic markers, and myocilin in HTM cells. These characteristics of Hic-5 in TM cells indicate its importance in regulation of AH outflow through the TM in both normal and glaucomatous eyes.

Duke Scholars

Published In

Invest Ophthalmol Vis Sci

DOI

EISSN

1552-5783

Publication Date

August 2015

Volume

56

Issue

9

Start / End Page

5656 / 5669

Location

United States

Related Subject Headings

  • Trabecular Meshwork
  • Signal Transduction
  • RNA
  • Ophthalmology & Optometry
  • LIM Domain Proteins
  • Intracellular Signaling Peptides and Proteins
  • Immunohistochemistry
  • Immunoblotting
  • Humans
  • Glycoproteins
 

Citation

APA
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ICMJE
MLA
NLM
Pattabiraman, P. P., & Rao, P. V. (2015). Hic-5 Regulates Actin Cytoskeletal Reorganization and Expression of Fibrogenic Markers and Myocilin in Trabecular Meshwork Cells. Invest Ophthalmol Vis Sci, 56(9), 5656–5669. https://doi.org/10.1167/iovs.15-17204
Pattabiraman, Padmanabhan Paranji, and Ponugoti Vasantha Rao. “Hic-5 Regulates Actin Cytoskeletal Reorganization and Expression of Fibrogenic Markers and Myocilin in Trabecular Meshwork Cells.Invest Ophthalmol Vis Sci 56, no. 9 (August 2015): 5656–69. https://doi.org/10.1167/iovs.15-17204.
Pattabiraman, Padmanabhan Paranji, and Ponugoti Vasantha Rao. “Hic-5 Regulates Actin Cytoskeletal Reorganization and Expression of Fibrogenic Markers and Myocilin in Trabecular Meshwork Cells.Invest Ophthalmol Vis Sci, vol. 56, no. 9, Aug. 2015, pp. 5656–69. Pubmed, doi:10.1167/iovs.15-17204.

Published In

Invest Ophthalmol Vis Sci

DOI

EISSN

1552-5783

Publication Date

August 2015

Volume

56

Issue

9

Start / End Page

5656 / 5669

Location

United States

Related Subject Headings

  • Trabecular Meshwork
  • Signal Transduction
  • RNA
  • Ophthalmology & Optometry
  • LIM Domain Proteins
  • Intracellular Signaling Peptides and Proteins
  • Immunohistochemistry
  • Immunoblotting
  • Humans
  • Glycoproteins