ArticleiScience2024
Activation of limbal epithelial proliferation is partly controlled by the ACE2-LCN2 pathway.
Article in iScience, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
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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
9 citing papers in PubMed.
- Intradermal priming to intravesical Bacillus Calmette-Guérin in non-muscle invasive bladder cancer: A translational research and phase I clinical trial.Oncology research · 2025Trial
- Ocular Surface Inflammation as a Driver of Cornea Limbal Stem Cell Deficiency: Mechanisms and Implications.International journal of molecular sciences · 2026Review
- Losartan Alleviates Chemical Burn-Induced Limbal Stem Cell Deficiency: Repurposing a Venerable Anti-Hypertension Drug.Investigative ophthalmology & visual science · 2026Article
- PAX6 Deficiency Compromises the Ability of Limbal Epithelial Stem Cells to Properly Differentiate Into Mature Corneal Epithelial Cells.Investigative ophthalmology & visual science · 2026Article
- Article
- Inhibitor of DNA-Binding 3 Is a Novel Regulator of Limbal Epithelial Cell Migration Via the EphA2/Akt Signaling Pathway.Investigative ophthalmology & visual science · 2025Article
- IFITM1/OVOL1 Axis Is a Novel Regulator of the Expansion of the Limbal Epithelial Stem/Early Transient Amplifying Cell Population.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2025Article
- Recent Advances in Stem Cells of Corneal Epithelia.Investigative ophthalmology & visual science · 2025Review
- Transparent GelMA biomaterials: Advanced solutions for ocular tissue engineering and regenerative ophthalmology.Advances in ophthalmology practice and researchReview
Corrections and comments
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Authors and funding
14 authors.
Funding
Abstract
In response to corneal injury, an activation of corneal epithelial stem cells and their direct progeny the early transit amplifying (eTA) cells to rapidly proliferate is critical for proper re-epithelialization. Thus, it is important to understand how such stem/eTA cell activation is regulated. Angiotensin-converting enzyme 2 (ACE2) is predominantly expressed in the stem/eTA-enriched limbal epithelium but its role in the limbal epithelium was unclear. Single cell RNA sequencing (scRNA-seq) suggested that Ace2 involved the proliferation of the stem/eTA cells. Ace2 was reduced following corneal injury. Such reduction enhanced limbal epithelial proliferation and downregulated LCN2, a negative regulator of proliferation in a variety of tissues, via upregulating TGFA and consequently activating epidermal growth factor receptor (EGFR). Inhibition of EGFR or overexpression of LCN2 reversed the increased proliferation in limbal epithelial cells lacking ACE2. Our findings demonstrate that after corneal injury, ACE2 is downregulated, which activates limbal epithelial cell proliferation via a TGFA/EGFR/LCN2 pathway.
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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.