ArticleInvestigative ophthalmology & visual science2013
Triple combination of siRNAs targeting TGFβ1, TGFβR2, and CTGF enhances reduction of collagen I and smooth muscle actin in corneal fibroblasts.
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 20 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
20 citing papers in PubMed, 33 citations in OpenAlex.
- The Genetic and Epigenetic Architecture of Keratoconus: Emerging Pathways and Clinical Implications.Genes · 2026Review
- Bioactive materials forBioactive materials · 2024Review
- Transcriptional profiling specifies the pathogen-specific human host response to infectious keratitis.Frontiers in cellular and infection microbiology · 2023Article
- Review
- Different Modulatory Effects of Four Methicillin-ResistantBiomolecules · 2021Article
- Crowdsourced Identification of Potential Target Genes for CTV Induced Gene Silencing for Controlling the Citrus Greening VectorFrontiers in physiology · 2021Article
- Thrombospondin-1: A Key Protein That Induces Fibrosis in Diabetic Complications.Journal of diabetes research · 2020Review
- The future of canine glaucoma therapy.Veterinary ophthalmology · 2019Review
- Corneal chemical burn treatment through a delivery system consisting of TGF-βDrug delivery and translational research · 2018Article
- Differential Expression of Coding and Long Noncoding RNAs in Keratoconus-Affected Corneas.Investigative ophthalmology & visual science · 2018Article
- Development of wound healing models to study TGFβ3's effect on SMA.Experimental eye research · 2017Article
- Dual-Phase Iontophoresis for the Delivery of Antisense Oligonucleotides.Nucleic acid therapeutics · 2017Article
- PDGFRα Is a Key Regulator of T1 and T3's Differential Effect on SMA Expression in Human Corneal Fibroblasts.Investigative ophthalmology & visual science · 2017Article
- Connective tissue growth factor is not necessary for haze formation in excimer laser wounded mouse corneas.PloS one · 2017Article
- Decorin reduces hypertrophic scarring through inhibition of the TGF-β1/Smad signaling pathway in a rat osteomyelitis model.Experimental and therapeutic medicine · 2016Article
- Nanolayered siRNA delivery platforms for local silencing of CTGF reduce cutaneous scar contraction in third-degree burns.Biomaterials · 2016Article
- Technologies for controlled, local delivery of siRNA.Journal of controlled release : official journal of the Controlled Release Society · 2015Review
- Assessment of anti-scarring therapies in ex vivo organ cultured rabbit corneas.Experimental eye research · 2014Article
- Reversal of fibrosis by TGF-β3 in a 3D in vitro model.Experimental eye research · 2014Article
- Cornea As a Model for Testing CTGF-Based Antiscarring Drugs.Bone and tissue regeneration insightsArticle
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
purposeTransforming growth factor β1 (TGFβ1), TGFβ receptor (TGFβR2), and connective tissue growth factor (CTGF) are key regulators of fibrosis in the cornea and in other tissues, including liver, skin, and kidney. We developed an antifibrotic treatment targeting these three critical scarring genes by using a combination of small interfering RNAs (siRNAs) and assessed its effect on downstream scarring genes, collagen I, and α smooth muscle actin (SMA).
methodsUp to six individual siRNAs for each of the three target gene mRNAs were transfected into cultures of rabbit corneal fibroblasts at concentrations from 15 to 90 nM. The knockdown of target gene proteins was measured by ELISA, and the two most effective siRNAs were tested in dual combinations. Knockdown percentages of both individual and dual siRNA combinations were analyzed for synergy by using combination index to predict "effective" and "ineffective" triple siRNA combinations. Effects of both triple siRNA combinations on target and downstream mRNAs were measured by using quantitative RT-PCR, and levels of SMA protein were assessed by immunohistochemistry.
resultsSingle and dual siRNA combinations produced a wide range of protein knockdown of target genes (5%-80%). The effective triple siRNA combination significantly reduced mRNA levels of target genes (>80%) and downstream scarring genes (>85%), and of SMA protein (>95%), and significantly reduced cell migration without reducing cell viability.
conclusionsSimultaneous targeting of TGFβ1, TGFβR2, and CTGF genes by effective triple siRNA combination produced high knockdown of target and downstream scarring genes without cell toxicity, which may have clinical applications in reducing corneal fibrosis and scarring in other tissues.
Indexed as
Identifiers
What OpenQuestion holds
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.