ArticleCellular signalling2015
The autotaxin-LPA2 GPCR axis is modulated by γ-irradiation and facilitates DNA damage repair.
Article in Cellular signalling, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 29 papers.
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Who cites it
29 citing papers in PubMed, 47 citations in OpenAlex.
- In vivo effects of dexamethasone on blood gene expression in ataxia telangiectasia.Molecular and cellular biochemistry · 2018Trial
- GPCR systems coordinate cellular resilience against aging-associated stress.Frontiers in molecular biosciences · 2026Review
- Decoding lysophosphatidic acid signaling in physiology and disease: mapping the multimodal and multinodal signaling networks.Signal transduction and targeted therapy · 2025Review
- The Effect of Ionizing Irradiation on the Autotaxin-Lysophasphatidic Acid Axis and Interleukin-6/8 Secretion in Different Breast Cancer Cell Lines.Journal of personalized medicine · 2024Article
- Roles of lysophosphatidic acid (LPA) receptor-mediated signaling in cancer cell biology.Journal of bioenergetics and biomembranes · 2024Review
- Gastrointestinal Acute Radiation Syndrome: Mechanisms, Models, Markers, and Medical Countermeasures.Radiation research · 2024Article
- N-acetyl-L-tryptophan (NAT) provides protection to intestinal epithelial cells (IEC-6) against radiation-induced apoptosis via modulation of oxidative stress and mitochondrial membrane integrity.Molecular biology reports · 2023Article
- E2F7 drives autotaxin/Enpp2 transcription via chromosome looping: Repression by p53 in murine but not in human carcinomas.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2023Article
- Emerging roles of lysophosphatidic acid receptor subtype 5 (LPAR5) in inflammatory diseases and cancer.Pharmacology & therapeutics · 2023Review
- Understanding the mechanisms underlying obesity in remodeling the breast tumor immune microenvironment: from the perspective of inflammation.Cancer biology & medicine · 2023Review
- High-throughput screening strategies for space-based radiation countermeasure discovery.Life sciences in space research · 2022Review
- Review
- Activation of G protein coupled estrogen receptor prevents chemotherapy-induced intestinal mucositis by inhibiting the DNA damage in crypt cell in an extracellular signal-regulated kinase 1- and 2- dependent manner.Cell death & disease · 2021Article
- Revisiting the role of lysophosphatidic acid in stem cell biology.Experimental biology and medicine (Maywood, N.J.) · 2021Review
- Review
- Dysregulation of lysophospholipid signaling by p53 in malignant cells and the tumor microenvironment.Cellular signalling · 2021Review
- Lipids in the tumor microenvironment: From cancer progression to treatment.Progress in lipid research · 2020Review
- Role of Adipose Tissue-Derived Autotaxin, Lysophosphatidate Signaling, and Inflammation in the Progression and Treatment of Breast Cancer.International journal of molecular sciences · 2020Review
- Review
- Article
Corrections and comments
- Erratum issuedBanerje, Souvik [corrected to Banerjee, Souvik]
Authors and funding
17 authors at 3 institutions in 1 country.
Funding
Abstract
In this study we characterized the effects of radiation injury on the expression and function of the autotaxin (ATX)-LPA2 GPCR axis. In IEC-6 crypt cells and jejunum enteroids quantitative RT-PCR showed a time- and dose-dependent upregulation of lpa2 in response to γ-irradiation that was abolished by mutation of the NF-κB site in the lpa2 promoter or by inhibition of ATM/ATR kinases with CGK-733, suggesting that lpa2 is a DNA damage response gene upregulated by ATM via NF-κB. The resolution kinetics of the DNA damage marker γ-H2AX in LPA-treated IEC-6 cells exposed to γ-irradiation was accelerated compared to vehicle, whereas pharmacological inhibition of LPA2 delayed the resolution of γ-H2AX. In LPA2-reconstituted MEF cells lacking LPA1&3 the levels of γ-H2AX decreased rapidly, whereas in Vector MEF were high and remained sustained. Inhibition of ERK1&2 or PI3K/AKT signaling axis by pertussis toxin or the C311A/C314A/L351A mutation in the C-terminus of LPA2 abrogated the effect of LPA on DNA repair. LPA2 transcripts in Lin(-)Sca-1(+)c-Kit(+) enriched for bone marrow stem cells were 27- and 5-fold higher than in common myeloid or lymphoid progenitors, respectively. Furthermore, after irradiation higher residual γ-H2AX levels were detected in the bone marrow or jejunum of irradiated LPA2-KO mice compared to WT mice. We found that γ-irradiation increases plasma ATX activity and LPA level that is in part due to the previously established radiation-induced upregulation of TNFα. These findings identify ATX and LPA2 as radiation-regulated genes that appear to play a physiological role in DNA repair.
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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 Socratic graph.