ArticleFibrogenesis & tissue repair2012
Discoidin domain receptors regulate the migration of primary human lung fibroblasts through collagen matrices.
Article in Fibrogenesis & tissue repair, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 44 citations in OpenAlex.
- Whole genome analyses of a well-differentiated liposarcoma reveals novel SYT1 and DDR2 rearrangements.PloS one · 2014Trial
- Decoding collagen cues: the interplay of integrins and discoidin domain receptors in health and disease.Journal of biomedical science · 2026Review
- Dual roles of DDR1 in stromal remodeling and immune escape: a regulator of the tumor immune microenvironment.Frontiers in immunology · 2026Review
- A Novel Mutation inArchives of Iranian medicine · 2025Article
- Recent Advances in the Development and Application of Cell-Loaded Collagen Scaffolds.International journal of molecular sciences · 2025Review
- Exploring IRGs as a Biomarker of Pulmonary Hypertension Using Multiple Machine Learning Algorithms.Diagnostics (Basel, Switzerland) · 2024Article
- Investigation of Cell Mechanics and Migration on DDR2-Expressing Neuroblastoma Cell Line.Life (Basel, Switzerland) · 2024Article
- Collagen Type XI Inhibits Lung Cancer-Associated Fibroblast Functions and Restrains the Integrin Binding Site Availability on Collagen Type I Matrix.International journal of molecular sciences · 2022Article
- Inhibition of DDR1 reduces invasive features of human A375 melanoma, HT29 colon carcinoma and SK-HEP hepatoma cells.Cell adhesion & migration · 2020Article
- Silencing of sinusoidal DDR1 reduces murine liver metastasis by colon carcinoma.Scientific reports · 2020Article
- Fibroblasts in the Tumor Microenvironment: Shield or Spear?International journal of molecular sciences · 2018Review
- Targeting of Discoidin Domain Receptor 2 (DDR2) Prevents Myofibroblast Activation and Neovessel Formation During Pulmonary Fibrosis.Molecular therapy : the journal of the American Society of Gene Therapy · 2016Article
- Tissue turnover of collagen type I, III and elastin is elevated in the PCLS model of IPF and can be restored back to vehicle levels using a phosphodiesterase inhibitor.Respiratory research · 2016Article
- Matrix metalloproteinases as therapeutic targets for idiopathic pulmonary fibrosis.American journal of respiratory cell and molecular biology · 2015Review
- Novel insights into the function and dynamics of extracellular matrix in liver fibrosis.American journal of physiology. Gastrointestinal and liver physiology · 2015Review
- Hematopoietic Origin of Murine Lung Fibroblasts.Stem cells international · 2015Article
- Endocytosis of collagen by hepatic stellate cells regulates extracellular matrix dynamics.American journal of physiology. Cell physiology · 2014Article
- Discoidin domain receptor 2 germline gene deletion leads to altered heart structure and function in the mouse.American journal of physiology. Heart and circulatory physiology · 2014Article
- Discoidin domain receptor 1 contributes to tumorigenesis through modulation of TGFBI expression.PloS one · 2014Article
- Using functional signature ontology (FUSION) to identify mechanisms of action for natural products.Science signaling · 2013Article
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
backgroundThe two discoidin domain receptors (DDRs), DDR1 and DDR2 are receptor tyrosine kinases (RTKs) with the unique ability among RTKs to respond to collagen. We have previously shown that collagen I induces DDR1 and matrix metalloproteinase (MMP)-10 expression through DDR2 activation and a Janus kinase (JAK)2 and extracellular signal-regulated kinase (ERK)1/2-mediated mechanism in primary human lung fibroblasts suggesting that these signaling pathways play a role in fibroblast function. Fibroblasts can traverse basement membrane barriers during development, wound healing and pathological conditions such as cancer and fibrosis by activating tissue-invasive programs, the identity of which remain largely undefined. In the present work, we investigated the role of DDRs and DDR-associated signal transduction in these processes.
resultsTranswell migration experiments showed that normal human lung fibroblast (NHLF) transmigration through collagen I-coated inserts is mediated by DDR2 and the DDR2-associated signaling kinases JAK2 and ERK1/2, but not DDR1. Additionally, experiments with specific small interfering (si)RNAs revealed that collagen I-induced expression of MMP-10 and MMP-2 is DDR2 but not DDR1 dependent in NHLFs. Our data showed that collagen I increases NHLF migration through collagen IV, the main component of basement membranes. Furthermore, basal and collagen I-induced NHLF migration through collagen IV-coated inserts was both DDR2 and DDR1 dependent. Finally, DDR2, but not DDR1 was shown to be involved in fibroblast proliferation.
conclusionsOur results suggest a mechanism by which the presence of collagen I in situations of excessive matrix deposition could induce fibroblast migration through basement membranes through DDR2 activation and subsequent DDR1 and MMP-2 gene expression. This work provides new insights into the role of DDRs in fibroblast function.
Identifiers
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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.