ArticleArchives of pharmacal research2022
Renal tubular PAR2 promotes interstitial fibrosis by increasing inflammatory responses and EMT process.
Article in Archives of pharmacal research, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers, 1 of them a synthesis that pooled it.
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
21 citing papers in PubMed, 1 synthesis or guideline pooled it, 28 citations in OpenAlex.
- Maternal Separation and Negative Renal Programming, Evidence of Morphofunctional Alterations in Rodent Models: Systematic Review and Meta-Analysis.International journal of molecular sciences · 2025Pooled it
- Proteinase-Activated Receptor 2 (PAR2) Deficiency and Cardiovascular Regulation: Context-Dependent Effects on Inflammation and Fibrosis.Current issues in molecular biology · 2026Review
- Atrial Fibrillation and Great Saphenous Vein Insufficiency: Exploration of Common Pathways in Hemodynamic Derangements and Systemic Inflammation.Reviews in cardiovascular medicine · 2026Review
- Article
- Poricoic Acid A attenuated TGF-β1-induced epithelial-mesenchymal transition in renal tubular epithelial cells through SPRY2/ERK signaling pathway.The Korean journal of physiology & pharmacology : official journal of the Korean Physiological Society and the Korean Society of Pharmacology · 2025Article
- The Role of PAR2 in MASLD Progression and HCC Development.International journal of molecular sciences · 2025Review
- Serine proteases and protease-activated receptors signaling in the kidney.American journal of physiology. Cell physiology · 2025Review
- Eicosapentaenoic Acid Modulates TGF-β1/Smad3/ILK Pathway to Attenuate Renal Fibrosis: A Biotechnological Approach.Iranian journal of biotechnology · 2025Article
- The Many Faces of Protease-Activated Receptor 2 in Kidney Injury.Biomedicines · 2025Review
- Gender Differences in Adenine Diet-Induced Kidney Toxicity: The Impact of 17β-Estradiol on Renal Inflammation and Fibrosis.International journal of molecular sciences · 2025Article
- Yiqi Juanshen decoction alleviates renal interstitial fibrosis by targeting the LOXL2/PI3K/AKT pathway to suppress EMT and inflammation.Scientific reports · 2025Article
- G protein-coupled receptor-mediated renal fibrosis: a key focus on kidney disease drug development.Frontiers in pharmacology · 2025Review
- Natural products in traditional Chinese medicine for renal fibrosis: a comprehensive review.Frontiers in pharmacology · 2025Review
- Renal Fibrosis: SIRT1 Still of Value.Biomedicines · 2024Review
- Knockdown of lncRNA MALAT1 attenuates renal interstitial fibrosis through miR-124-3p/ITGB1 axis.Scientific reports · 2023Article
- TLR7 activation by miR-21 promotes renal fibrosis by activating the pro-inflammatory signaling pathway in tubule epithelial cells.Cell communication and signaling : CCS · 2023Article
- 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
- Mesenchymal stem cells enhance CCL8 expression by podocytes in lupus-prone MRL.FasScientific reports · 2023Article
- Dapagliflozin alleviates renal fibrosis in a mouse model of adenine-induced renal injury by inhibiting TGF-β1/MAPK mediated mitochondrial damage.Frontiers in pharmacology · 2023Article
- Tissue Factor, Thrombosis, and Chronic Kidney Disease.Biomedicines · 2022Review
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
Renal fibrosis is defined by excessive extracellular matrix (ECM) accumulation and is associated with a decreased kidney function. Increased inflammation and infiltration of inflammatory cells are the key features of renal fibrosis development; however, the mechanism of how inflammation starts is still un-known. Here, we show that the activation of epithelial Protease-activating receptor 2 (PAR2) signaling plays an important role in the initiation of inflammation via increased chemokine expression and inflammatory cell induction. In the adenine diet-induced renal fibrosis mouse model, PAR2 expression was significantly increased in the renal tubule region. Kidneys from PAR2-knockout mice were protected from adenine diet-induced renal fibrosis, kidney dysfunction, and inflammation. Using NRK52E kidney epithelial cells, we further elucidated the mechanisms underlying these processes. Activation of PAR2 signaling pathway by PAR2 agonist specifically increased the levels of chemokines, including MCP1 and MCP3, via the MAPK-NF-κB signaling pathway. Inhibition of the MAPK signaling pathway attenuated PAR2 agonist-induced NF-κB activation, chemokine expression, and macrophage cell induction. Furthermore, PAR2 activation directly increased mesenchymal cell markers in epithelial cells. Taken together, we found that increased PAR2 expression and the PAR2/MAPK signaling pathway promote renal fibrosis by increasing the inflammatory responses and promoting EMT process.
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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.