ArticleInvestigative ophthalmology & visual science2009
Regulation of cross-linked actin network (CLAN) formation in human trabecular meshwork (HTM) cells by convergence of distinct beta1 and beta3 integrin pathways.
Article in Investigative ophthalmology & visual science, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 58 papers.
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Who cites it
58 citing papers in PubMed, 71 citations in OpenAlex.
- Modeling of Lowe Patient-Derived Induced Pluripotent Stem Cells Into Trabecular Meshwork.American journal of ophthalmology · 2026Article
- Cross-linked actin networks (CLANs) and their role in the trabecular meshwork.Experimental eye research · 2026Review
- Isobaric quantitative proteomics reveals altered extracellular matrix, cytoskeletal, and degradation pathways in glaucomatous trabecular meshwork cells.Scientific reports · 2026Article
- CD47 signaling in aging and age-related diseases: mechanisms, challenges, and therapeutic opportunities.Biogerontology · 2025Review
- Characterization, Enrichment, and Computational Modeling of Cross-Linked Actin Networks in Transformed Trabecular Meshwork Cells.Investigative ophthalmology & visual science · 2025Article
- A switch from α5β1 to αvβ3 integrin activity contributes to the development of a profibrotic mesenchymal phenotype in trabecular meshwork cells.Frontiers in cell and developmental biology · 2025Article
- Mechanobiology in the eye.npj biological physics and mechanics · 2025Review
- Characterization, enrichment, and computational modeling of cross-linked actin networks in trabecular meshwork cells.bioRxiv : the preprint server for biology · 2024Article
- Glucocorticoid-Induced Ocular Hypertension and Glaucoma.Clinical ophthalmology (Auckland, N.Z.) · 2024Review
- Estrogen dysregulation, intraocular pressure, and glaucoma risk.Experimental eye research · 2023Review
- Role of integrins in the development of fibrosis in the trabecular meshwork.Frontiers in ophthalmology · 2023Review
- TIPARP is involved in the regulation of intraocular pressure.Communications biology · 2022Article
- Thrombospondin 1 missense alleles induce extracellular matrix protein aggregation and TM dysfunction in congenital glaucoma.The Journal of clinical investigation · 2022Article
- Cross-linked actin networks (CLANs) affect stiffness and/or actin dynamics in transgenic transformed and primary human trabecular meshwork cells.Experimental eye research · 2022Article
- Pathogenesis of glaucoma: Extracellular matrix dysfunction in the trabecular meshwork-A review.Clinical & experimental ophthalmology · 2022Review
- A20 Attenuates the Fibrotic Response in the Trabecular Meshwork.International journal of molecular sciences · 2022Article
- Overexpression of Laminin 5Journal of oncology · 2022Article
- Thrombospondin-1 Signaling Through the Calreticulin/LDL Receptor Related Protein 1 Axis: Functions and Possible Roles in Glaucoma.Frontiers in cell and developmental biology · 2022Review
- Integrin Crosstalk and Its Effect on the Biological Functions of the Trabecular Meshwork/Schlemm's Canal.Frontiers in cell and developmental biology · 2022Review
- Article
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
purposeTo determine the beta1/beta3 integrin-mediated pathways that regulate cross-linked actin network (CLAN) formation in human trabecular meshwork (HTM) cells. CLANs form in glaucomatous and steroid-treated TM cells, which may contribute to reducing outflow facility through the TM.
methodsExpression of CD47 (an alphavbeta3 integrin coreceptor/thrombospondin-1 receptor) and integrins alphavbeta3 and beta1 was assessed by FACS. CLANs were induced by plating cells on fibronectin (a beta1 integrin ligand) in the absence or presence of the beta3 integrin-activating mAb AP-5 and were identified by phalloidin labeling. The role of Src kinases, PI-3 kinase (PI-3K), Rac1, and CD47 was determined by incubating cells with the inhibitors PP2 and EPA (Src kinases), LY294002 (PI-3K), or NSC23766 (Rac1). Tiam1 and Trio siRNAs and dominant-negative Tiam1 were used to determine which Rac1-specific guanine nucleotide exchange factor was involved. The role of CD47 was determined using the thrombospondin-1-derived agonist peptide 4N1K and the CD47 function blocking antibody B6H12.2.
resultsHTM cells expressed CD47 and integrins alphavbeta3 and beta1. beta3 Integrin or CD47 activation significantly increased CLAN formation over beta1 integrin-induced levels, whereas anti-CD47 mAb B6H12.2 inhibited this increase. PP2, NSC23766, and Trio siRNA decreased beta3-induced CLAN formation by 72%, 45%, and 67%, respectively, whereas LY294002 and dominant negative Tiam1 had no effect. LY294002 decreased beta1 integrin-mediated CLAN formation by 42%, and PP2 completely blocked it.
conclusionsDistinct beta1 and alphavbeta3 integrin signaling pathways converge to enhance CLAN formation. beta1-Mediated CLAN formation was PI-3K dependent, whereas beta3-mediated CLAN formation was CD47 and Rac1/Trio dependent and might have been regulated by thrombospondin-1. Both integrin pathways were Src dependent.
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