ArticleJournal of molecular medicine (Berlin, Germany)2019
Substance P induces fibrotic changes through activation of the RhoA/ROCK pathway in an in vitro human corneal fibrosis model.
Article in Journal of molecular medicine (Berlin, Germany), 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers, 1 of them a synthesis that pooled it.
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Who cites it
17 citing papers in PubMed, 1 synthesis or guideline pooled it, 27 citations in OpenAlex.
- The role of fibrosis in endometriosis: a systematic review.Human reproduction update · 2024Pooled it
- Macrophage Extracellular Vesicles: Therapeutic Strategies for Corneal Fibrosis in Rare Diseases.Biomolecules · 2026Review
- Biomaterial-assisted neuralization strategies for tissue engineering applications.Materials today. Bio · 2026Review
- Choroidal Mast Cells and Their Degranulation Are a Pivotal Trigger for Myopia Development.Investigative ophthalmology & visual science · 2025Article
- Down-Regulation of OncogeneInternational journal of molecular sciences · 2025Article
- A Comprehensive Review of the Role of Rho-Kinase Inhibitors in Corneal Diseases.Life (Basel, Switzerland) · 2025Review
- Selective Up-Regulation of Tumor Suppressor Gene Retinoblastoma by Bisacridine Derivative Through Gene Promoter Quadruplex Structures for Cancer Treatment.International journal of molecular sciences · 2025Article
- Effects of Cell Seeding Density, Extracellular Matrix Composition, and Geometry on Yes-Associated Protein Translocation in Corneal Fibroblasts.International journal of molecular sciences · 2025Article
- Review
- Substance P promotes the progression of bronchial asthma through activating the PI3K/AKT/NF-κB pathway mediated cellular inflammation and pyroptotic cell death in bronchial epithelial cells.Cell cycle (Georgetown, Tex.) · 2022Article
- Frontiers in Lichen Planopilaris and Frontal Fibrosing Alopecia Research: Pathobiology Progress and Translational Horizons.JID innovations : skin science from molecules to population health · 2022Review
- Ferulic Acid Combined With Bone Marrow Mesenchymal Stem Cells Attenuates the Activation of Hepatic Stellate Cells and Alleviates Liver Fibrosis.Frontiers in pharmacology · 2022Article
- Activation of NF-κB signaling via cytosolic mitochondrial RNA sensing in kerotocytes with mitochondrial DNA common deletion.Scientific reports · 2021Article
- Safety and efficacy of combination of suberoylamilide hydroxyamic acid and mitomycin C in reducing pro-fibrotic changes in human corneal epithelial cells.Scientific reports · 2021Article
- Herb-Partitioned Moxibustion Improves Crohn's Disease-Associated Intestinal Fibrosis by Suppressing the RhoA/ROCK1/MLC Pathway.Evidence-based complementary and alternative medicine : eCAM · 2021Article
- Acetylcholine decreases formation of myofibroblasts and excessive extracellular matrix production in an in vitro human corneal fibrosis model.Journal of cellular and molecular medicine · 2020Article
- Gelam honey promotes ex vivo corneal fibroblasts wound healing.Cytotechnology · 2019Article
Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Fibrosis is characterized by hardening, overgrowth, and development of scars in various tissues as a result of faulty reparative processes, diseases, or chronic inflammation. During the fibrotic process in the corneal stroma of the eye, the resident cells called keratocytes differentiate into myofibroblasts, specialized contractile fibroblastic cells that produce excessive amounts of disorganized extracellular matrix (ECM) and pro-fibrotic components such as alpha-smooth muscle actin (α-SMA) and fibronectin. This study aimed to elucidate the role of substance P (SP), a neuropeptide that has been shown to be involved in corneal wound healing, in ECM production and fibrotic markers expression in quiescent human keratocytes, and during the onset of fibrosis in corneal fibroblasts, in an in vitro human corneal fibrosis model. We report that SP induces keratocyte contraction and upregulates gene expression of collagens I, III, and V, and fibrotic markers: α-SMA and fibronectin, in keratocytes. Using our in vitro human corneal fibrosis model, we show that SP enhances gene expression and secretion of collagens I, III, and V, and lumican. Moreover, SP upregulates gene expression and secretion of α-SMA and fibronectin, and increases contractility of corneal fibroblasts during the onset of fibrosis. Activation of the preferred SP receptor, the neurokinin-1 receptor (NK-1R), is necessary for the SP-induced pro-fibrotic changes. In addition, SP induces the pro-fibrotic changes through activation of the RhoA/ROCK pathway. Taken together, we show that SP has a pro-fibrotic effect in both quiescent human keratocytes and during the onset of fibrosis in an in vitro human corneal fibrosis model.
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