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LPAR2 receptor activation attenuates radiation-induced disruption of apical junctional complexes and mucosal barrier dysfunction in mouse colon.
FASEB J. 2020 Jul 12 [Online ahead of print]FJ

Abstract

The tight junction (TJ) and barrier function of colonic epithelium is highly sensitive to ionizing radiation. We evaluated the effect of lysophosphatidic acid (LPA) and its analog, Radioprotein-1, on γ-radiation-induced colonic epithelial barrier dysfunction using Caco-2 and m-ICC12 cell monolayers in vitro and mice in vivo. Mice were subjected to either total body irradiation (TBI) or partial body irradiation (PBI-BM5). Intestinal barrier function was assessed by analyzing immunofluorescence localization of TJ proteins, mucosal inulin permeability, and plasma lipopolysaccharide (LPS) levels. Oxidative stress was analyzed by measuring protein thiol oxidation and antioxidant mRNA. In Caco-2 and m-ICC12 cell monolayers, LPA attenuated radiation-induced redistribution of TJ proteins, which was blocked by a Rho-kinase inhibitor. In mice, TBI and PBI-BM5 disrupted colonic epithelial tight junction and adherens junction, increased mucosal permeability, and elevated plasma LPS; TJ disruption by TBI was more severe in Lpar2-/- mice compared to wild-type mice. RP1, administered before or after irradiation, alleviated TBI and PBI-BM5-induced TJ disruption, barrier dysfunction, and endotoxemia accompanied by protein thiol oxidation and downregulation of antioxidant gene expression, cofilin activation, and remodeling of the actin cytoskeleton. These data demonstrate that LPAR2 receptor activation prevents and mitigates γ-irradiation-induced colonic mucosal barrier dysfunction and endotoxemia.

Authors+Show Affiliations

Department of Physiology, College of Medicine, University of Tennessee Health Science Center, Memphis, TN, USA.Department of Physiology, College of Medicine, University of Tennessee Health Science Center, Memphis, TN, USA.Department of Physiology, College of Medicine, University of Tennessee Health Science Center, Memphis, TN, USA.Department of Physiology, College of Medicine, University of Tennessee Health Science Center, Memphis, TN, USA.Department of Physiology, College of Medicine, University of Tennessee Health Science Center, Memphis, TN, USA.Department of Physiology, College of Medicine, University of Tennessee Health Science Center, Memphis, TN, USA.INSERM U773, Centre de Recherche Biomédicale, Bichat-Beaujon, CRB3, UFR de Médecine, Paris Cedex 18, France.Department of Physiology, College of Medicine, University of Tennessee Health Science Center, Memphis, TN, USA.Department of Physiology, College of Medicine, University of Tennessee Health Science Center, Memphis, TN, USA.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

32654268

Citation

Shukla, Pradeep K., et al. "LPAR2 Receptor Activation Attenuates Radiation-induced Disruption of Apical Junctional Complexes and Mucosal Barrier Dysfunction in Mouse Colon." FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology, 2020.
Shukla PK, Meena AS, Gangwar R, et al. LPAR2 receptor activation attenuates radiation-induced disruption of apical junctional complexes and mucosal barrier dysfunction in mouse colon. FASEB J. 2020.
Shukla, P. K., Meena, A. S., Gangwar, R., Szabo, E., Balogh, A., Chin Lee, S., Vandewalle, A., Tigyi, G., & Rao, R. (2020). LPAR2 receptor activation attenuates radiation-induced disruption of apical junctional complexes and mucosal barrier dysfunction in mouse colon. FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology. https://doi.org/10.1096/fj.202000544R
Shukla PK, et al. LPAR2 Receptor Activation Attenuates Radiation-induced Disruption of Apical Junctional Complexes and Mucosal Barrier Dysfunction in Mouse Colon. FASEB J. 2020 Jul 12; PubMed PMID: 32654268.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - LPAR2 receptor activation attenuates radiation-induced disruption of apical junctional complexes and mucosal barrier dysfunction in mouse colon. AU - Shukla,Pradeep K, AU - Meena,Avtar S, AU - Gangwar,Ruchika, AU - Szabo,Erzsebet, AU - Balogh,Andrea, AU - Chin Lee,Sue, AU - Vandewalle,Alain, AU - Tigyi,Gabor, AU - Rao,RadhaKrishna, Y1 - 2020/07/12/ PY - 2020/03/09/received PY - 2020/05/28/revised PY - 2020/06/15/accepted PY - 2020/7/13/entrez PY - 2020/7/13/pubmed PY - 2020/7/13/medline KW - endotoxemia KW - intestine KW - irradiation KW - lysophosphatidic acid KW - tight junction JF - FASEB journal : official publication of the Federation of American Societies for Experimental Biology JO - FASEB J. N2 - The tight junction (TJ) and barrier function of colonic epithelium is highly sensitive to ionizing radiation. We evaluated the effect of lysophosphatidic acid (LPA) and its analog, Radioprotein-1, on γ-radiation-induced colonic epithelial barrier dysfunction using Caco-2 and m-ICC12 cell monolayers in vitro and mice in vivo. Mice were subjected to either total body irradiation (TBI) or partial body irradiation (PBI-BM5). Intestinal barrier function was assessed by analyzing immunofluorescence localization of TJ proteins, mucosal inulin permeability, and plasma lipopolysaccharide (LPS) levels. Oxidative stress was analyzed by measuring protein thiol oxidation and antioxidant mRNA. In Caco-2 and m-ICC12 cell monolayers, LPA attenuated radiation-induced redistribution of TJ proteins, which was blocked by a Rho-kinase inhibitor. In mice, TBI and PBI-BM5 disrupted colonic epithelial tight junction and adherens junction, increased mucosal permeability, and elevated plasma LPS; TJ disruption by TBI was more severe in Lpar2-/- mice compared to wild-type mice. RP1, administered before or after irradiation, alleviated TBI and PBI-BM5-induced TJ disruption, barrier dysfunction, and endotoxemia accompanied by protein thiol oxidation and downregulation of antioxidant gene expression, cofilin activation, and remodeling of the actin cytoskeleton. These data demonstrate that LPAR2 receptor activation prevents and mitigates γ-irradiation-induced colonic mucosal barrier dysfunction and endotoxemia. SN - 1530-6860 UR - https://www.unboundmedicine.com/medline/citation/32654268/LPAR2_receptor_activation_attenuates_radiation-induced_disruption_of_apical_junctional_complexes_and_mucosal_barrier_dysfunction_in_mouse_colon L2 - https://doi.org/10.1096/fj.202000544R DB - PRIME DP - Unbound Medicine ER -
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