ArticleInvestigative ophthalmology & visual science2014
Pharmacological regulation of SPARC by lovastatin in human trabecular meshwork cells.
Article in Investigative ophthalmology & visual science, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 24 citations in OpenAlex.
- Remodeling of the Lamina Cribrosa: Mechanisms and Potential Therapeutic Approaches for Glaucoma.International journal of molecular sciences · 2022Review
- Statins Inhibit the Gliosis of MIO-M1, a Müller Glial Cell Line Induced by TRPV4 Activation.International journal of molecular sciences · 2022Article
- RETRACTED: Neuroprotective Effect of Statins in a Rat Model of Chronic Ocular Hypertension.International journal of molecular sciences · 2021Article
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- [Rho kinase inhibitors as new local therapy option in primary open angle glaucoma].Der Ophthalmologe : Zeitschrift der Deutschen Ophthalmologischen Gesellschaft · 2021Review
- Statins Suppress TGF-β2-Mediated MMP-2 and MMP-9 Expression and Activation Through RhoA/ROCK Inhibition in Astrocytes of the Human Optic Nerve Head.Investigative ophthalmology & visual science · 2020Article
- Identification of Gene Changes Induced by Dexamethasone in the Anterior Segment of the Human Eye Using Bioinformatics Analysis.Medical science monitor : international medical journal of experimental and clinical research · 2019Article
- Association of Daily Dosage and Type of Statin Agent With Risk of Open-Angle Glaucoma.JAMA ophthalmology · 2017Article
- Smoc2 potentiates proliferation of hepatocellular carcinoma cellsWorld journal of gastroenterology · 2016Article
- Rho GTPase signaling promotes constitutive expression and release of TGF-β2 by human trabecular meshwork cells.Experimental eye research · 2016Article
- Association Between Statin Use and Open-angle Glaucoma in Hyperlipidemia Patients: A Taiwanese Population-based Case-control Study.Medicine · 2015 · on this mapObservational
- Matricellular proteins in the trabecular meshwork: review and update.Journal of ocular pharmacology and therapeutics : the official journal of the Association for Ocular Pharmacology and Therapeutics · 2014Review
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
purposeStatins have been shown to increase aqueous outflow facility. The matricellular protein SPARC (secreted protein acidic and rich in cysteine) is a critical mediator of aqueous outflow and intraocular pressure (IOP). Here, we examine the effects of lovastatin on SPARC expression in trabecular meshwork (TM) cells, exploring the molecular mechanisms involved.
methodsPrimary cultured human TM cells were incubated for 24, 48, and 72 hours with 10 μM lovastatin. In separate cultures, media was supplemented with either farnesyl pyrophosphate (FPP) or geranylgeranyl pyrophosphate (GGPP) for the duration of the 72-hour time point experiment. Trabecular meshwork cells were also pretreated for 24 hours with lovastatin followed by 24-hour stimulation with 3 ng/mL TGF-β2. Cell lysates and media were harvested and relative mRNA and protein level changes were determined. Krüppel-like factor 4 (KLF4) localization in normal human anterior segments was examined by immunofluorescence. Adenovirus expressing human KLF4 was used and relative changes in SPARC mRNA and protein levels were assessed.
resultsIncubating TM cells with lovastatin suppressed SPARC mRNA and protein levels. This effect was reversed upon media supplementation with GGPP but not FPP. Pretreating cells with lovastatin inhibited TGF-β2 induction of SPARC. The KLF4 transcription factor was expressed throughout the TM and the inner and outer walls of Schlemm's canal. Lovastatin treatment upregulated KLF4 mRNA and protein levels. Overexpression of KLF4 downregulated SPARC expression.
conclusionsCollectively, our data identify lovastatin as an important pharmacological suppressor of SPARC expression in TM cells, and provide further insight into the molecular mechanisms mediating statin enhancement of aqueous outflow facility.
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