ArticleThe Journal of biological chemistry2013
Lacritin rescues stressed epithelia via rapid forkhead box O3 (FOXO3)-associated autophagy that restores metabolism.
Article in The Journal of biological chemistry, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT06854393 (Lacripep, a Novel Investigational Agent, for Corneal Wound Healing and Ocular Surface Homeostasis), which is not on this map. Cited by 38 papers, 3 of them syntheses that pooled it.
What it found
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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.
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.
Lacripep, a Novel Investigational Agent, for Corneal Wound Healing and Ocular Surface Homeostasis
Who cites it
38 citing papers in PubMed, 3 syntheses or guidelines pooled it, 52 citations in OpenAlex.
- The role of autophagy in ocular health: mechanisms, pathologies, and therapeutic strategies.Biology direct · 2026Pooled it
- Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition)Autophagy · 2021Guideline
- Guidelines for the use and interpretation of assays for monitoring autophagy (3rd edition).Autophagy · 2016Guideline
- Site-specific O-glycans influence lacritin structure and multimerization in tears.Protein science : a publication of the Protein Society · 2026Article
- Distinctive Lacritin Cleavage-Potentiated Bactericidal Alteration of thebioRxiv : the preprint server for biology · 2026Article
- Mapping galectin-3 ligands in human tear fluid establishes spliceoform-dependent lacritin binding.Communications biology · 2026Article
- Autophagy is required for the development and functionality of lacrimal gland-like organoids.Stem cell reports · 2026Article
- Lacritin cleavage-potentiated targeting of iron - respiratory reciprocity promotes bacterial death.The Journal of biological chemistry · 2025Article
- Ocular surface glycocalyx in health and disease.Frontiers in cell and developmental biology · 2025Review
- Pathological Mechanisms of Particulate Matter-Mediated Ocular Disorders: A Review.International journal of molecular sciences · 2024Review
- The Impact of Aging on Ocular Diseases: Unveiling Complex Interactions.Aging and disease · 2024Review
- Targeting Iron - Respiratory Reciprocity Promotes Bacterial Death.bioRxiv : the preprint server for biology · 2024Article
- Desmocollin-1 is associated with pro-metastatic phenotype of luminal A breast cancer cells and is modulated by parthenolide.Cellular & molecular biology letters · 2023Article
- Autophagy in dry eye disease: Therapeutic implications of autophagy modulators on the ocular surface.Indian journal of ophthalmology · 2023Review
- The roles of autophagy and mitophagy in corneal pathology: current knowledge and future perspectives.Frontiers in medicine · 2023Review
- Autophagy in the normal and diseased cornea.Experimental eye research · 2022Review
- The Role of Endogenous Antimicrobial Peptides in Modulating Innate Immunity of the Ocular Surface in Dry Eye Diseases.International journal of molecular sciences · 2021Review
- Targeting autophagy to overcome drug resistance: further developments.Journal of hematology & oncology · 2020Review
- The Lacritin-Syndecan-1-Heparanase Axis in Dry Eye Disease.Advances in experimental medicine and biology · 2020Review
- Development of lacrimal gland inflammation in the mouse model of herpes stromal keratitis.Experimental eye research · 2019Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
9 authors at 5 institutions in 4 countries.
Funding
Abstract
Homeostasis is essential for cell survival. However, homeostatic regulation of surface epithelia is poorly understood. The eye surface, lacking the cornified barrier of skin, provides an excellent model. Tears cover the surface of the eye and are deficient in dry eye, the most common eye disease affecting at least 5% of the world's population. Only a tiny fraction of the tear proteome appears to be affected, including lacritin, an epithelium-selective mitogen that promotes basal tearing when topically applied to rabbit eyes. Here we show that homeostasis of cultured corneal epithelia is entirely lacritin-dependent and elucidate the mechanism as a rapid autophagic flux to promptly restore cellular metabolism and mitochondrial fusion in keeping with the short residence time of lacritin on the eye. Accelerated flux appears to be derived from lacritin-stimulated acetylation of FOXO3 as a novel ligand for ATG101 and coupling of stress-acetylated FOXO1 with ATG7 (which remains uncoupled without lacritin) and be sufficient to selectively divert huntingtin mutant Htt103Q aggregates largely without affecting non-aggregated Htt25Q. This is in keeping with stress as a prerequisite for lacritin-stimulated autophagy. Lacritin targets the cell surface proteoglycan syndecan-1 via its C-terminal amino acids Leu(108)-Leu(109)-Phe(112) and is also available in saliva, plasma, and lung lavage. Thus, lacritin may promote epithelial homeostasis widely.
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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.