ArticleThe American journal of pathology2012
Lysophosphatidic acid increases proximal tubule cell secretion of profibrotic cytokines PDGF-B and CTGF through LPA2- and Gαq-mediated Rho and αvβ6 integrin-dependent activation of TGF-β.
Article in The American journal of pathology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 55 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
55 citing papers in PubMed, 95 citations in OpenAlex.
- Insights into the binding mechanism and structural requirements of LPAR2 antagonists as antifibrotic agents based on homology modeling, molecular docking, prediction of membrane permeability and 3D QSAR.Journal of computer-aided molecular design · 2026Article
- The core mechanism of hypertension-linked renal fibrosis: "RAAS-ROS-inflammation-fibrosis" axis.iScience · 2026Review
- ATF3 aggravates kidney fibrosis via HDAC6-dependent epigenetic reprogramming.International journal of biological sciences · 2026Article
- Decoding lysophosphatidic acid signaling in physiology and disease: mapping the multimodal and multinodal signaling networks.Signal transduction and targeted therapy · 2025Review
- Bone Marrow Mononuclear Cells Administration Restore Lysophosphatidic Acid (LPA) Levels and Cellular Signaling Axis in Rats Submitted to Renal Ischemia-Reperfusion.International journal of molecular sciences · 2025Article
- PRDM16 acts as a homeostasis regulation factor to suppress the transition of AKI to CKD via upregulation of eukaryotic initiation factor 6.Cellular and molecular life sciences : CMLS · 2025Article
- Smad transcription factors as mediators of 7 transmembrane G protein-coupled receptor signalling.Acta pharmacologica Sinica · 2025Review
- Inhibition of tubular epithelial cells ferroptosis alleviates renal interstitial fibrosis by reducing lipid hydroperoxides and TGF-β/Smad signaling.Cell communication and signaling : CCS · 2025Article
- Effects of short- and long-term use of propolis extracts on liver and kidney in rats.Food science & nutrition · 2024Article
- Transforming growth factor-β receptors: versatile mechanisms of ligand activation.Acta pharmacologica Sinica · 2024Review
- Drugs targeting CTGF in the treatment of pulmonary fibrosis.Journal of cellular and molecular medicine · 2024Review
- Lineage tracing reveals transient phenotypic adaptation of tubular cells during acute kidney injury.iScience · 2024Article
- The Effect of Anti-Autotaxin Aptamers on the Development of Proliferative Vitreoretinopathy.International journal of molecular sciences · 2023Article
- Kidney fibrosis: from mechanisms to therapeutic medicines.Signal transduction and targeted therapy · 2023Review
- Tubular cells produce FGF2 via autophagy after acute kidney injury leading to fibroblast activation and renal fibrosis.Autophagy · 2023Article
- Crosstalk between proximal tubular epithelial cells and other interstitial cells in tubulointerstitial fibrosis after renal injury.Frontiers in endocrinology · 2023Review
- From AKI to CKD: Maladaptive Repair and the Underlying Mechanisms.International journal of molecular sciences · 2022Review
- Lysophosphatidic Acid Is a Proinflammatory Stimulus of Renal Tubular Epithelial Cells.International journal of molecular sciences · 2022Article
- Admission Lysophosphatidic Acid Is Related to Impaired Kidney Function in Acute Aortic Dissection: 2-Year Retrospective Follow-Up Study.Frontiers in cardiovascular medicine · 2022Article
- Targeting Ferroptosis Attenuates Interstitial Inflammation and Kidney Fibrosis.Kidney diseases (Basel, Switzerland) · 2022Article
Corrections and comments
- Commented on by
Authors and funding
9 authors at 5 institutions in 2 countries.
Funding
Abstract
After ischemia-reperfusion injury (IRI), kidney tubules show activated transforming growth factor β (TGF-β) signaling and increased expression of profibrotic peptides, platelet-derived growth factor-B (PDGF-B) and connective tissue growth factor (CTGF). If tubule repair after IRI is incomplete, sustained paracrine activity of these peptides can activate interstitial fibroblast progenitors and cause fibrosis. We show that lysophosphatidic acid (LPA), a ubiquitous phospholipid that is increased at sites of injury and inflammation, signals through LPA2 receptors and Gαq proteins of cultured proximal tubule cells to transactivate latent TGF-β in a Rho/Rho-kinase and αvβ6 integrin-dependent manner. Active TGF-β peptide then initiates signaling to increase the production and secretion of PDGF-B and CTGF. In a rat model of IRI, increased TGF-β signaling that was initiated early during reperfusion did not subside during recovery, but progressively increased, causing tubulointerstitial fibrosis. This was accompanied by correspondingly increased LPA2 and β6 integrin proteins and elevated tubule expression of TGF-β1, together with PDGF-B and CTGF. Treatment with a pharmacological TGF-β type I receptor antagonist suppressed TGF-β signaling, decreased the expression of β6 integrin, PDGF-B, and CTGF, and ameliorated fibrosis. We suggest that LPA-initiated autocrine signaling is a potentially important mechanism that gives rise to paracrine profibrotic signaling in injured kidney tubule cells.
Indexed as
Identifiers
What OpenQuestion holds
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.