Skip to main content
Journal cover image

Glypican-4 regulated actin cytoskeletal reorganization in glucocorticoid treated trabecular meshwork cells and involvement of Wnt/PCP signaling.

Publication ,  Journal Article
Maddala, R; Eldawy, C; Bachman, W; Soderblom, EJ; Rao, PV
Published in: J Cell Physiol
March 2023

A common adverse response to the clinical use of glucocorticoids (GCs) is elevated intraocular pressure (IOP) which is a major risk factor for glaucoma. Elevated IOP arises due to impaired outflow of aqueous humor (AH) through the trabecular meshwork (TM). Although GC-induced changes in actin cytoskeletal dynamics, contractile characteristics, and cell adhesive interactions of TM cells are believed to influence AH outflow and IOP, the molecular mechanisms mediating changes in these cellular characteristics are poorly understood. Our studies focused on evaluating changes in the cytoskeletal and cytoskeletal-associated protein (cytoskeletome) profile of human TM cells treated with dexamethasone (Dex) using label-free mass spectrometric quantification, identified elevated levels of specific proteins known to regulate actin stress fiber formation, contraction, actin networks crosslinking, cell adhesion, and Wnt signaling, including LIMCH1, ArgBP2, CNN3, ITGBL1, CTGF, palladin, FAT1, DIAPH2, EPHA4, SIPA1L1, and GPC4. Several of these proteins colocalized with the actin cytoskeleton and underwent alterations in distribution profile in TM cells treated with Dex, and an inhibitor of Abl/Src kinases. Wnt/Planar Cell Polarity (PCP) signaling agonists-Wnt5a and 5b were detected prominently in the cytoskeletome fraction of TM cells, and studies using siRNA to suppress expression of glypican-4 (GPC4), a known modulator of the Wnt/PCP pathway revealed that GPC4 deficiency impairs Dex induced actin stress fiber formation, and activation of c-Jun N-terminal Kinase (JNK) and Rho kinase. Additionally, while Dex augmented, GPC4 deficiency suppressed the formation of actin stress fibers in TM cells in the presence of Dex and Wnt5a. Taken together, these results identify the GPC4-dependent Wnt/PCP signaling pathway as one of the crucial upstream regulators of Dex induced actin cytoskeletal reorganization and cell adhesion in TM cells, opening an opportunity to target the GPC4/Wnt/PCP pathway for treatment of ocular hypertension in glaucoma.

Duke Scholars

Altmetric Attention Stats
Dimensions Citation Stats

Published In

J Cell Physiol

DOI

EISSN

1097-4652

Publication Date

March 2023

Volume

238

Issue

3

Start / End Page

631 / 646

Location

United States

Related Subject Headings

  • rho-Associated Kinases
  • Wnt Signaling Pathway
  • Trabecular Meshwork
  • Stress Fibers
  • Intraocular Pressure
  • Humans
  • Glypicans
  • Glucocorticoids
  • Glaucoma
  • Dexamethasone
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Maddala, R., Eldawy, C., Bachman, W., Soderblom, E. J., & Rao, P. V. (2023). Glypican-4 regulated actin cytoskeletal reorganization in glucocorticoid treated trabecular meshwork cells and involvement of Wnt/PCP signaling. J Cell Physiol, 238(3), 631–646. https://doi.org/10.1002/jcp.30953
Maddala, Rupalatha, Camelia Eldawy, William Bachman, Erik J. Soderblom, and Ponugoti V. Rao. “Glypican-4 regulated actin cytoskeletal reorganization in glucocorticoid treated trabecular meshwork cells and involvement of Wnt/PCP signaling.J Cell Physiol 238, no. 3 (March 2023): 631–46. https://doi.org/10.1002/jcp.30953.
Maddala R, Eldawy C, Bachman W, Soderblom EJ, Rao PV. Glypican-4 regulated actin cytoskeletal reorganization in glucocorticoid treated trabecular meshwork cells and involvement of Wnt/PCP signaling. J Cell Physiol. 2023 Mar;238(3):631–46.
Maddala, Rupalatha, et al. “Glypican-4 regulated actin cytoskeletal reorganization in glucocorticoid treated trabecular meshwork cells and involvement of Wnt/PCP signaling.J Cell Physiol, vol. 238, no. 3, Mar. 2023, pp. 631–46. Pubmed, doi:10.1002/jcp.30953.
Maddala R, Eldawy C, Bachman W, Soderblom EJ, Rao PV. Glypican-4 regulated actin cytoskeletal reorganization in glucocorticoid treated trabecular meshwork cells and involvement of Wnt/PCP signaling. J Cell Physiol. 2023 Mar;238(3):631–646.
Journal cover image

Published In

J Cell Physiol

DOI

EISSN

1097-4652

Publication Date

March 2023

Volume

238

Issue

3

Start / End Page

631 / 646

Location

United States

Related Subject Headings

  • rho-Associated Kinases
  • Wnt Signaling Pathway
  • Trabecular Meshwork
  • Stress Fibers
  • Intraocular Pressure
  • Humans
  • Glypicans
  • Glucocorticoids
  • Glaucoma
  • Dexamethasone