ArticleThe American journal of pathology2010
An Akt- and Fra-1-dependent pathway mediates platelet-derived growth factor-induced expression of thrombomodulin, a novel regulator of smooth muscle cell migration.
Article in The American journal of pathology, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 26 citations in OpenAlex.
- Multiomics analysis unveils an inosine-sensitive DNA damage response in neurogenic bladder after spinal cord injury.JCI insight · 2025Article
- Investigation of the impact of bromodomain inhibition on cytoskeleton stability and contraction.Cell communication and signaling : CCS · 2024Article
- Investigation of the impact of bromodomain inhibition on cytoskeleton stability and contraction.bioRxiv : the preprint server for biology · 2023Article
- PDGFR-β signaling mediates HMGB1 release in mechanically stressed vascular smooth muscle cells.PloS one · 2022Article
- AKT2 regulates endothelial-mediated coagulation homeostasis and promotes intrathrombotic recanalization and thrombus resolution in a mouse model of venous thrombosis.Journal of thrombosis and thrombolysis · 2020Article
- The chondroitin sulfate moiety mediates thrombomodulin-enhanced adhesion and migration of vascular smooth muscle cells.Journal of biomedical science · 2018Article
- Deletion of neuropilin 2 enhances detrusor contractility following bladder outlet obstruction.JCI insight · 2017Article
- New Amniotic Membrane Based Biocomposite for Future Application in Reconstructive Urology.PloS one · 2016Article
- Dynamic reciprocity in cell-scaffold interactions.Advanced drug delivery reviews · 2015Review
- Integration of proteomic and transcriptomic profiles identifies a novel PDGF-MYC network in human smooth muscle cells.Cell communication and signaling : CCS · 2014Article
- Loss of Sh3gl2/endophilin A1 is a common event in urothelial carcinoma that promotes malignant behavior.Neoplasia (New York, N.Y.) · 2013Article
- Mechanical stretch increases MMP-2 production in vascular smooth muscle cells via activation of PDGFR-β/Akt signaling pathway.PloS one · 2013Article
- Article
- Large oncosomes in human prostate cancer tissues and in the circulation of mice with metastatic disease.The American journal of pathology · 2012Article
- Increased smooth muscle contractility in mice deficient for neuropilin 2.The American journal of pathology · 2012Article
- Inhibition of TNF-α improves the bladder dysfunction that is associated with type 2 diabetes.Diabetes · 2012Article
- FosB regulates stretch-induced expression of extracellular matrix proteins in smooth muscle.The American journal of pathology · 2011Article
- FOSL1 is integral to establishing the maternal-fetal interface.Molecular and cellular biology · 2011Article
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
Overdistension of hollow organs evokes pathological changes characterized by smooth muscle remodeling. Mechanical stimuli induce smooth muscle cell (SMC) growth through acute activation of signaling cascades and by increased expression of soluble mitogens. Physical forces have also been implicated in ligand-independent activation of receptor tyrosine kinases, including the platelet-derived growth factor (PDGF) receptor, although the extent to which this occurs in intact tissue is unknown. Previously, we implicated Akt and activator protein-1 (AP-1) as mediators of growth and gene expression in SMC exposed to cyclic stretch or PDGF. Here we show that bladder wall distension leads to PDGFR activation and identify thrombomodulin (TM) as an Akt and AP-1 target in SMC. We demonstrate that TM, also induced by bladder stretch injury, is regulated at the transcriptional level by the AP-1 components c-jun and Fra1. Mutation of an AP-1 motif at -2010/-2004 abolished both AP-1 binding and PDGF responsiveness of the TM promoter. Fra1 silencing diminished PDGF-induced TM expression and SMC cell cycle transit. In contrast, TM knockdown did not affect cell growth but attenuated PDGF-stimulated SMC migration. Taken together, these results reveal new facets of TM regulation in SMC and provide the first demonstration of a role for endogenous TM in PDGF-induced cell migration. Moreover, TM induction on bladder injury suggests that it may be a biomarker for pathological smooth muscle remodeling.
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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.