ArticleInvestigative ophthalmology & visual science2013
Regulation of SPARC by transforming growth factor β2 in human trabecular meshwork.
Article in Investigative ophthalmology & visual science, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
24 citing papers in PubMed, 42 citations in OpenAlex.
- Integrin-Linked Kinase Suppression Reduces SPARC's Effect on Intraocular Pressure and Extracellular Matrix.Investigative ophthalmology & visual science · 2026Article
- Pro-Homeostatic Effects of Estrogen on Intraocular Pressure and the Trabecular Meshwork.Investigative ophthalmology & visual science · 2026Article
- TRPV4 activation by TGFβ2 enhances cellular contractility and drives ocular hypertension.eLife · 2025Article
- Article
- Review
- Review
- SPARC: a potential target for functional nanomaterials and drugs.Frontiers in molecular biosciences · 2023Review
- Effect of SPARC Suppression in Mice, Perfused Human Anterior Segments, and Trabecular Meshwork Cells.Investigative ophthalmology & visual science · 2022Article
- Pathogenesis of glaucoma: Extracellular matrix dysfunction in the trabecular meshwork-A review.Clinical & experimental ophthalmology · 2022Review
- Review
- Secreted protein acidic and rich in cysteine (SPARC) knockout mice have greater outflow facility.PloS one · 2020Article
- Aqueous humor levels of TGFβ2 and SFRP1 in different types of glaucoma.BMC ophthalmology · 2019Article
- Epigenetics and Signaling Pathways in Glaucoma.BioMed research international · 2017Review
- Elevation of intraocular pressure in rodents using viral vectors targeting the trabecular meshwork.Experimental eye research · 2015Review
- Secreted Protein Acidic and Rich in Cysteine in Ocular Tissue.Journal of ocular pharmacology and therapeutics : the official journal of the Association for Ocular Pharmacology and Therapeutics · 2015Review
- p38 MAP kinase inhibitor suppresses transforming growth factor-β2-induced type 1 collagen production in trabecular meshwork cells.PloS one · 2015Article
- Canonical wnt signaling regulates extracellular matrix expression in the trabecular meshwork.Investigative ophthalmology & visual science · 2014Article
- Primary cilia signaling mediates intraocular pressure sensation.Proceedings of the National Academy of Sciences of the United States of America · 2014Article
- 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
- Differential gene expression in glaucoma.Cold Spring Harbor perspectives in medicine · 2014Review
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Authors and funding
4 authors at 3 institutions in 2 countries.
Funding
Abstract
purposeAn increased aqueous level of TGF-β2 has been found in many primary open-angle glaucoma patients. Secreted Protein, Acidic, and Rich in Cysteine (SPARC)-null mice have a lower intraocular pressure. The mechanistic relationship between SPARC and TGF-β2 in trabecular meshwork (TM) is unknown. We hypothesized that TGF-β2 upregulates SPARC expression in TM.
methodsCultured TM cells were incubated with selective inhibitors for p38 MAP kinase (p38), Smad3, p42, JNK, RhoA, PI3K, or TGF-β2 receptor for 2 hours, and then TGF-β2 was added for 24 hours in serum-free media. Quantitative polymerase chain reaction (qPCR) and immunoblot analysis were performed. Immunofluorescent microscopy was used to determine nuclear translocation of signaling proteins. Ad5.hSPARC and Lentiviral shRNA for p38 and Smad3 were constructed, and infected human TM cells.
resultsSPARC was upregulated by TGF-β2 in the human TM cells (3.8 ± 1.7-fold, n = 6, P = 0.01 for protein and 7.1 ± 3.7-fold, n = 6, P = 0.01 for mRNA), while upregulation of SPARC had no effect on TGF-β2. TGF-β2-induced SPARC expression was suppressed by inhibitors against p38 (-40.3 ± 20.9%, n = 10, P = 0.0001), Smad3 (-56.2 ± 18.9%, n = 10, P = 0.0001), JNK (-49.1 ± 24.6%, n = 10, P = 0.0001), and TGF-β2 receptor (-83.6 ± 14.4%, n = 6, P = 0.003). Phosphorylation and translocation of Smad3, p38, and MAPKAPK2 were detected at 30 minutes and 1 hour, respectively, following TGF-β2 treatment. Phosphorylation of JNK and c-jun was detected before TGF-β2 treatment. SPARC was suppressed 31 ± 13% (n = 5, P < 0.0001) by shRNA-p38 and 41 ± 3% (n = 5, P < 0.0001) by shRNA-Smad3.
conclusionsTGF-β2 upregulates SPARC expression in human TM through Smad-dependent (Smad2/3) or -independent (p38) signaling pathways. SPARC may be a downstream regulatory node of TGF-β2-mediated IOP elevation.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.