ArticleThe Journal of biological chemistry2013
Proteinase-activated receptor-2 transactivation of epidermal growth factor receptor and transforming growth factor-β receptor signaling pathways contributes to renal fibrosis.
Article in The Journal of biological chemistry, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 58 papers.
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Who cites it
58 citing papers in PubMed, 93 citations in OpenAlex.
- Novel Molecular Signatures of Peripheral Regulatory T Cells in Kidney Disease Associated with Type 1 Diabetes.Kidney360 · 2026Article
- Role of the protease-activated receptor 2 in multi-walled carbon nanotube-induced macrophage polarizationFrontiers in toxicology · 2026Article
- G protein-coupled receptors as novel therapeutic targets in non-small-cell lung cancer.Medical review (2021) · 2025Review
- Hepatocyte KCTD17-mediated SERPINA3 inhibition determines liver fibrosis in metabolic dysfunction-associated steatohepatitis.Experimental & molecular medicine · 2025Article
- Smad transcription factors as mediators of 7 transmembrane G protein-coupled receptor signalling.Acta pharmacologica Sinica · 2025Review
- Protease-activated receptor-2 (PAR2) mutation attenuates airway fibrosis in mice during the exacerbation of house dust mite‑induced allergic lung disease by multi‑walled carbon nanotubes.Respiratory research · 2025Article
- The Many Faces of Protease-Activated Receptor 2 in Kidney Injury.Biomedicines · 2025Review
- Comparative Cardioprotective Effectiveness: NOACs vs. Nattokinase-Bridging Basic Research to Clinical Findings.Biomolecules · 2024Review
- Tissue Inhibitor of Metalloproteinases-2 (TIMP-2) as a Prognostic Biomarker in Acute Kidney Injury: A Narrative Review.Diagnostics (Basel, Switzerland) · 2024Review
- An essential signaling cascade for avian auditory hair cell regeneration.Developmental cell · 2024Article
- Interaction of estradiol and renin-angiotensin system with microRNAs-21 and -29 in renal fibrosis: focus on TGF-β/smad signaling pathway.Molecular biology reports · 2024Review
- PAR2 activation on human tubular epithelial cells engages converging signaling pathways to induce an inflammatory and fibrotic milieu.Frontiers in pharmacology · 2024Article
- Targeting the epidermal growth factor receptor (EGFR/ErbB) for the potential treatment of renal pathologies.Frontiers in pharmacology · 2024Review
- Association between early coagulation disorders and the risk of severe acute kidney injury in traumatic brain injury patients: a retrospective cohort study using the MIMIC-IV database.Frontiers in neurology · 2024Article
- Role of the protease-activated receptor-2 (PAR2) in the exacerbation of house dust mite-induced murine allergic lung disease by multi-walled carbon nanotubes.Particle and fibre toxicology · 2023Article
- Article
- Tissue Factor, Thrombosis, and Chronic Kidney Disease.Biomedicines · 2022Review
- Diversification of PAR signaling through receptor crosstalk.Cellular & molecular biology letters · 2022Review
- The innate immune response, microenvironment proteinases, and the COVID-19 pandemic: pathophysiologic mechanisms and emerging therapeutic targets.Kidney international supplements · 2022Review
- Renal tubular PAR2 promotes interstitial fibrosis by increasing inflammatory responses and EMT process.Archives of pharmacal research · 2022Article
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Chronic kidney diseases cause significant morbidity and mortality in the population. During renal injury, kidney-localized proteinases can signal by cleaving and activating proteinase-activated receptor-2 (PAR2), a G-protein-coupled receptor involved in inflammation and fibrosis that is highly expressed in renal tubular cells. Following unilateral ureteric obstruction, PAR2-deficient mice displayed reduced renal tubular injury, fibrosis, collagen synthesis, connective tissue growth factor (CTGF), and α-smooth muscle actin gene expression at 7 days, compared with wild-type controls. In human proximal tubular epithelial cells in vitro, PAR2 stimulation with PAR2-activating peptide (PAR2-AP) alone significantly up-regulated the expression of CTGF, a potent profibrotic cytokine. The induction of CTGF by PAR2-AP was synergistically increased when combined with transforming growth factor-β (TGF-β). Consistent with these findings, treating human proximal tubular epithelial cells with PAR2-AP induced Smad2/3 phosphorylation in the canonical TGF-β signaling pathway. The Smad2 phosphorylation and CTGF induction required signaling via both the TGFβ-receptor and EGF receptor suggesting that PAR2 utilizes transactivation mechanisms to initiate fibrogenic signaling. Taken together, our data support the hypothesis that PAR2 synergizes with the TGFβ signaling pathway to contribute to renal injury and 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.