ArticleInvestigative ophthalmology & visual science2008
Association of protein tyrosine phosphatases (PTPs)-1B with c-Met receptor and modulation of corneal epithelial wound healing.
Article in Investigative ophthalmology & visual science, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers, 1 of them a synthesis that pooled it.
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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.
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Who cites it
29 citing papers in PubMed, 1 synthesis or guideline pooled it, 42 citations in OpenAlex.
- Pharmacological PTEN inhibition: potential clinical applications and effects in tissue regeneration.Regenerative medicine · 2020Pooled it
- SPARC Promotes Corneal Epithelial Wound Healing Through β-catenin Nuclear Translocation and c-Met Activation.Investigative ophthalmology & visual science · 2026Article
- Article
- Topical vanadate improves tensile strength and alters collagen organisation of excisional wounds in a mouse model.Wound repair and regeneration : official publication of the Wound Healing Society [and] the European Tissue Repair Society · 2023Article
- The role of protein tyrosine phosphatase 1B (PTP1B) in the pathogenesis of type 2 diabetes mellitus and its complications.Journal of physiology and biochemistry · 2022Review
- Novel function of THEMIS2 in the enhancement of cancer stemness and chemoresistance by releasing PTP1B from MET.Oncogene · 2022Article
- Wound healing of the corneal epithelium: a review.Asian biomedicine : research, reviews and news · 2021Review
- Systemic diseases and the cornea.Experimental eye research · 2021Review
- CAPN1 promotes malignant behavior and erlotinib resistance mediated by phosphorylation of c-Met and PIK3R2 via degrading PTPN1 in lung adenocarcinoma.Thoracic cancer · 2020Article
- Variable Responses to Corneal Grafts: Insights from Immunology and Systems Biology.Journal of clinical medicine · 2020Review
- Met inhibition revokes IFNγ-induction of PD-1 ligands in MET-amplified tumours.British journal of cancer · 2019Article
- An Update on Corneal Biomechanics and Architecture in Diabetes.Journal of ophthalmology · 2019Review
- Tyrosine dephosphorylated cortactin downregulates contractility at the epithelial zonula adherens through SRGAP1.Nature communications · 2017Article
- Diabetic complications in the cornea.Vision research · 2017Review
- GDF15 is a heart-derived hormone that regulates body growth.EMBO molecular medicine · 2017Article
- Beta Cell Formation in vivo Through Cellular Networking, Integration and Processing (CNIP) in Wild Type Adult Mice.Current pharmaceutical biotechnology · 2016Article
- Progress in corneal wound healing.Progress in retinal and eye research · 2015Review
- Differential effects of hepatocyte growth factor and keratinocyte growth factor on corneal epithelial cell cycle protein expression, cell survival, and growth.Molecular vision · 2014Article
- Emerging drugs for the treatment of diabetic ulcers.Expert opinion on emerging drugs · 2013Review
- Protein tyrosine phosphatase-1B regulates the tyrosine phosphorylation of the adapter Grb2-associated binder 1 (Gab1) in the retina.Cell communication and signaling : CCS · 2013Article
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
purposeThe purpose of this study was to investigate the expression and activity of protein tyrosine phosphatases (PTPs) in epithelium during corneal wound healing and to investigate how PTPs regulate activation of the c-Met receptor and the receptor's proximal signaling.
methodsRabbit corneas were injured by gentle scraping of the surface, leaving the limbal epithelium intact, and epithelium was collected at 1, 2, 3, and 7 days after injury. In organ culture models, epithelium was removed and corneas were incubated with hepatocyte growth factor (HGF), with or without the PTP inhibitor bpV(phen), and the PI-3K inhibitors wortmannin and LY294002. Human corneal epithelial (HCE) cells were stimulated with HGF with or without bpV(phen). Total cell lysates and cytosolic and membrane fractions were analyzed by Western blot. PTP activities were measured with specific substrates. PTP1B and SHP-2 genes were knocked down by interference RNA (siRNA).
resultsPTP activity and expression increased during wound healing. The most abundant were SHP-2, PTP1B, and PTEN. HGF activated the c-Met receptor in HCE cells up to 30 minutes and was downregulated by 2 hours. Inhibition of PTPs increased HGF-promoted wound healing, HGF-activated phosphorylation of c-Met, and its downstream signal PI-3K/Akt, but not ERK1/2 or p70S6K. PTP1B and SHP-2 were bound to the c-Met. Part of the c-Met was colocalized in the endoplasmic reticulum with PTP1B. PTP1B phosphorylation increased when the c-Met receptor was deactivated, and gene knockdown of PTP1B increased c-Met activation. SHP-2 phosphorylation and binding to c-Met was higher during receptor activation, and SHP-2 gene silencing decreased receptor phosphorylation.
conclusionsInhibition of PTP activity mimics the effect of HGF by activating the PI-3K/Akt signal involved in wound healing. PTP1B and SHP-2 are bound to the c-Met receptor to control its activity. Although the binding of PTP1B increases when there is a decrease in c-Met activation and acts as a negative regulator of the receptor, the increased binding and phosphorylation of SHP-2 coincide with maximal stimulation of c-Met, acting as a positive regulator.
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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.