ArticleThe Journal of clinical investigation2007
Tissue-type plasminogen activator promotes murine myofibroblast activation through LDL receptor-related protein 1-mediated integrin signaling.
Article in The Journal of clinical investigation, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 83 papers.
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.
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Who cites it
83 citing papers in PubMed, 113 citations in OpenAlex.
- Integrated RNA-Seq Profiling Identifies NRXN1+ Cell-Fibroblast Associated MAPK Signaling in Prurigo Nodularis.Allergy, asthma & immunology research · 2026Article
- Integrated Transcriptomic Analysis Suggests a C1Q-Related Macrophage-Fibroblast Signaling Axis in Keloids.International journal of molecular sciences · 2026Article
- Plasminogen Activation System and Fibroblasts: Impact on Tissue Remodeling, Disease, and Organ Homeostasis.Inflammation · 2026Review
- RNA-binding protein LARP6 coordinates hepatic stellate cell activation and liver fibrosis.The Journal of clinical investigation · 2026Article
- Abietane-Type Diterpenoids from the Resin ofMolecules (Basel, Switzerland) · 2026Article
- Roles of tissue plasminogen activator in chronic subdural hematoma, independent of the fibrinolytic system.Neurosurgical review · 2026Article
- Melatonin attenuates kidney injury by alleviating lysosomal damage in diabetic kidney disease.Acta biochimica et biophysica Sinica · 2025Article
- The winding road to platelet α-granules.Frontiers in cell and developmental biology · 2025Review
- Myofibroblast-derived exosomes enhance macrophages to myofibroblasts transition and kidney fibrosis.Renal failure · 2024Article
- Matrix metalloproteinases in kidney homeostasis and diseases: an update.American journal of physiology. Renal physiology · 2024Review
- Functions for platelet factor 4 (PF4/CXCL4) and its receptors in fibroblast-myofibroblast transition and fibrotic failure of arteriovenous fistulas (AVFs).The journal of vascular access · 2024Article
- Research progress on miR-124-3p in the field of kidney disease.BMC nephrology · 2024Review
- Novel insights into the multifaceted and tissue-specific roles of the endocytic receptor LRP1.The Journal of biological chemistry · 2024Review
- Dysregulated bidirectional epithelial-mesenchymal crosstalk: a core determinant of lung fibrosis progression.Chinese medical journal pulmonary and critical care medicine · 2024Article
- Macrophage Function Modulated by tPA Signaling in Mouse Experimental Kidney Disease Models.International journal of molecular sciences · 2023Review
- Article
- The uPA/uPAR System Orchestrates the Inflammatory Response, Vascular Homeostasis, and Immune System in Fibrosis Progression.International journal of molecular sciences · 2023Review
- CD44s-activated tPA/LRP1-NFκB pathway drives lamellipodia outgrowth in luminal-type breast cancer cells.Frontiers in cell and developmental biology · 2023Article
- TRPM7 restrains plasmin activity and promotes transforming growth factor-β1 signaling in primary human lung fibroblasts.Archives of toxicology · 2022Article
- Single-cell transcriptome analysis of regenerating RGCs reveals potent glaucoma neural repair genes.Neuron · 2022Article
23 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
The activation of interstitial fibroblasts to become alpha-SMA-positive myofibroblasts is an essential step in the evolution of chronic kidney fibrosis, as myofibroblasts are responsible for the production and deposition of the ECM components that are a hallmark of the disease. Here we describe a signaling pathway that leads to this activation. Tissue-type plasminogen activator (tPA) promoted TGF-beta1-mediated alpha-SMA and type I collagen expression in rat kidney interstitial fibroblasts. This fibrogenic effect was independent of its protease activity but required its membrane receptor, the LDL receptor-related protein 1 (LRP-1). In rat kidney fibroblasts, tPA induced rapid LRP-1 tyrosine phosphorylation and enhanced beta1 integrin recruitment by facilitating the LRP-1/beta1 integrin complex formation. Blockade or knockdown of beta1 integrin abolished type I collagen and alpha-SMA expression. Furthermore, inhibition of the integrin-linked kinase (ILK), a downstream effector of beta1 integrin, or disruption of beta1 integrin/ILK engagement, abrogated the tPA action, whereas ectopic expression of ILK mimicked tPA in promoting myofibroblast activation. In murine renal interstitium after obstructive injury, tPA and alpha-SMA colocalized with LRP-1, and tPA deficiency reduced LRP-1/beta1 integrin interaction and myofibroblast activation. These findings show that tPA induces LRP-1 tyrosine phosphorylation, which in turn facilitates the LRP-1-mediated recruitment of beta1 integrin and downstream ILK signaling, thereby leading to myofibroblast activation. This study implicates tPA as a fibrogenic cytokine that promotes the progression of kidney fibrosis.
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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.