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Mechanistic basis of Rho GTPase-induced extracellular matrix synthesis in trabecular meshwork cells.

Publication ,  Journal Article
Pattabiraman, PP; Rao, PV
Published in: Am J Physiol Cell Physiol
March 2010

Elevated intraocular pressure arising from impaired aqueous humor drainage through the trabecular pathway is a major risk factor for glaucoma. To understand the molecular basis for Rho GTPase-mediated resistance to aqueous humor drainage, we investigated the possible interrelationship between actomyosin contractile properties and extracellular matrix (ECM) synthesis in human trabecular meshwork (TM) cells expressing a constitutively active form of RhoA (RhoAV14). TM cells expressing RhoAV14 exhibited significant increases in fibronectin, tenascin C, laminin, alpha-smooth muscle actin (alpha-SMA) levels, and matrix assembly in association with increased actin stress fibers and myosin light-chain phosphorylation. RhoAV14-induced changes in ECM synthesis and actin cytoskeletal reorganization were mimicked by lysophosphatidic acid and TGF-beta(2), known to increase resistance to aqueous humor outflow and activate Rho/Rho kinase signaling. RhoAV14, lysophosphatidic acid, and TGF-beta(2) stimulated significant increases in Erk1/2 phosphorylation, paralleled by profound increases in fibronectin, serum response factor (SRF), and alpha-SMA expression. Treatment of RhoA-activated TM cells with inhibitors of Rho kinase or Erk, on the other hand, decreased fibronectin and alpha-SMA levels. Although suppression of SRF expression (both endogenous and RhoA, TGF-beta(2)-stimulated) via the use of short hairpin RNA decreased alpha-SMA levels, fibronectin was unaffected. Conversely, fibronectin induced alpha-SMA expression in an SRF-dependent manner. Collectively, data on RhoA-induced changes in actomyosin contractile activity, ECM synthesis/assembly, and Erk activation, along with fibronectin-induced alpha-SMA expression in TM cells, reveal a potential molecular interplay between actomyosin cytoskeletal tension and ECM synthesis/assembly. This interaction could be significant for the homeostasis of aqueous humor drainage through the pressure-sensitive trabecular pathway.

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Published In

Am J Physiol Cell Physiol

DOI

EISSN

1522-1563

Publication Date

March 2010

Volume

298

Issue

3

Start / End Page

C749 / C763

Location

United States

Related Subject Headings

  • rhoA GTP-Binding Protein
  • Transforming Growth Factor beta2
  • Transduction, Genetic
  • Trabecular Meshwork
  • Tenascin
  • Stress Fibers
  • Serum Response Factor
  • Recombinant Fusion Proteins
  • RNA Interference
  • Physiology
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Pattabiraman, P. P., & Rao, P. V. (2010). Mechanistic basis of Rho GTPase-induced extracellular matrix synthesis in trabecular meshwork cells. Am J Physiol Cell Physiol, 298(3), C749–C763. https://doi.org/10.1152/ajpcell.00317.2009
Pattabiraman, Padmanabhan P., and Ponugoti Vasantha Rao. “Mechanistic basis of Rho GTPase-induced extracellular matrix synthesis in trabecular meshwork cells.Am J Physiol Cell Physiol 298, no. 3 (March 2010): C749–63. https://doi.org/10.1152/ajpcell.00317.2009.
Pattabiraman PP, Rao PV. Mechanistic basis of Rho GTPase-induced extracellular matrix synthesis in trabecular meshwork cells. Am J Physiol Cell Physiol. 2010 Mar;298(3):C749–63.
Pattabiraman, Padmanabhan P., and Ponugoti Vasantha Rao. “Mechanistic basis of Rho GTPase-induced extracellular matrix synthesis in trabecular meshwork cells.Am J Physiol Cell Physiol, vol. 298, no. 3, Mar. 2010, pp. C749–63. Pubmed, doi:10.1152/ajpcell.00317.2009.
Pattabiraman PP, Rao PV. Mechanistic basis of Rho GTPase-induced extracellular matrix synthesis in trabecular meshwork cells. Am J Physiol Cell Physiol. 2010 Mar;298(3):C749–C763.

Published In

Am J Physiol Cell Physiol

DOI

EISSN

1522-1563

Publication Date

March 2010

Volume

298

Issue

3

Start / End Page

C749 / C763

Location

United States

Related Subject Headings

  • rhoA GTP-Binding Protein
  • Transforming Growth Factor beta2
  • Transduction, Genetic
  • Trabecular Meshwork
  • Tenascin
  • Stress Fibers
  • Serum Response Factor
  • Recombinant Fusion Proteins
  • RNA Interference
  • Physiology