ArticleInvestigative ophthalmology & visual science2012
Klf4 regulates the expression of Slurp1, which functions as an immunomodulatory peptide in the mouse cornea.
Article in Investigative ophthalmology & visual science, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
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Who cites it
33 citing papers in PubMed, 56 citations in OpenAlex.
- Trial
- The Secreted Ly6/uPAR-Related Protein-1 (SLURP1) Protects the Cornea From Oxidative Stress.Investigative ophthalmology & visual science · 2025Article
- Scalable production of recombinant three-finger proteins: from inclusion bodies to high quality molecular probes.Microbial cell factories · 2024Article
- The Secreted Ly6/uPAR-Related Protein 1 (Slurp1) Modulates Corneal Angiogenic Inflammation Via NF-κB Signaling.Investigative ophthalmology & visual science · 2024Article
- Aβ1-42 Accumulation Accompanies Changed Expression of Ly6/uPAR Proteins, Dysregulation of the Cholinergic System, and Degeneration of Astrocytes in the Cerebellum of Mouse Model of Early Alzheimer Disease.International journal of molecular sciences · 2023Article
- Molecular nature of ocular surface barrier function, diseases that affect it, and its relevance for ocular drug delivery.The ocular surface · 2023Review
- Selective targeting of α7 nicotinic acetylcholine receptor by synthetic peptide mimicking loop I of human SLURP-1 provides efficient and prolonged therapy of epidermoid carcinomaFrontiers in cell and developmental biology · 2023Article
- Review
- Secreted Ly-6/uPAR-related protein-1 (SLURP1) is a pro-differentiation factor that stalls G1-S transition during corneal epithelial cell cycle progression.The ocular surface · 2022Article
- High mRNA expression of LY6 gene family is associated with overall survival outcome in pancreatic ductal adenocarcinoma.Oncotarget · 2021Article
- Endogenous α7 nAChR Agonist SLURP1 FacilitatesFrontiers in immunology · 2021Article
- Identification and validation of a prognostic signature and combination drug therapy for immunotherapy of head and neck squamous cell carcinoma.Computational and structural biotechnology journal · 2021Article
- Recent Discoveries on the Involvement of Krüppel-Like Factor 4 in the Most Common Cancer Types.International journal of molecular sciences · 2020Review
- Conjunctival goblet cells: Ocular surface functions, disorders that affect them, and the potential for their regeneration.The ocular surface · 2020Review
- Glucosamine impedes transforming growth factor β1-mediated corneal fibroblast differentiation by targeting Krüppel-like factor 4.Journal of biomedical science · 2019Article
- The secreted Ly-6/uPAR related protein-1 (SLURP1) stabilizes epithelial cell junctions and suppresses TNF-α-induced cytokine production.Biochemical and biophysical research communications · 2019Article
- The secreted Ly6/uPAR-related protein-1 suppresses neutrophil binding, chemotaxis, and transmigration through human umbilical vein endothelial cells.Scientific reports · 2019Article
- Transformation of the Transcriptomic Profile of Mouse Periocular Mesenchyme During Formation of the Embryonic Cornea.Investigative ophthalmology & visual science · 2019Article
- Corneal Epithelial Cells Exhibit Myeloid Characteristics and Present Antigen via MHC Class II.Investigative ophthalmology & visual science · 2018Article
- Endogenous CHRNA7-ligand SLURP1 as a potential tumor suppressor and anti-nicotinic factor in pancreatic cancer.Oncotarget · 2018Article
Corrections and comments
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Authors and funding
7 authors at 4 institutions in 2 countries.
Funding
Abstract
purposeThe secreted Ly6/uPAR-related protein-1 (Slurp1), associated with the hyperkeratotic disorder mal de Meleda, is abundantly expressed in corneas. Here, we examine its corneal expression and functions.
methodsGene expression was quantified by quantitative PCR (qPCR), immunoblots, and immunofluorescent staining. Effect of Kruppel-like factor 4 (Klf4) on Slurp1 promoter was evaluated by chromatin immunoprecipitation (ChIP) and transient transfections. Adenoviral vectors were used to express Slurp1 in corneas. Leukocytic infiltration in bacterial lipopolysaccharide (LPS)-, herpes simplex virus type 1 (HSV-1)-, or adenovirus (serotype 5)-treated mouse corneas was characterized by flow cytometry.
resultsCorneal expression of Slurp1 increased sharply upon mouse eyelid opening, concurrent with the elevated expression of Klf4. Slurp1 was significantly decreased in Klf4 conditional null (Klf4CN) corneas that displayed elevated expression of cytokines and cytokine receptors, as well as neutrophil influx consistent with a proinflammatory environment. In additional models of corneal inflammation, Slurp1 expression was abrogated within 24 hours of LPS injection or HSV-1 or adenoviral infection, accompanied by a predominantly neutrophilic infiltrate. Neutrophilic infiltration was enhanced in HSV-1-infected Klf4CN corneas lacking Slurp1. SLURP1 promoter activity was stimulated by KLF4, suppressed by IL-4, IL-13, and TNFα, and unperturbed by IFN-γ. Slurp1 downregulation and neutrophil influx were comparable in HSV-1-infected wild-type (WT) and Ifng-/- mouse corneas. Mouse corneas infected with Slurp1-expressing adenoviral vectors displayed reduced signs of inflammation and restricted neutrophilic infiltration compared with those infected with control vectors.
conclusionsKlf4 regulates the expression of Slurp1, a key immunomodulatory peptide that is abundantly expressed in healthy corneas and is downregulated in proinflammatory conditions.
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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.