Group IVA Cytosolic Phospholipase A2 (cPLA2α): Pharmacological Inhibition Attenuates Kidney Inflammation and Fibrosis
6 affiliations
- 1Department of Biology, Norwegian University of Science and Technology, N-7491 Trondheim, Norway
- 2Renal Division, Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA 02115, USA
- 3Coegin Pharma AB, c/o Medicon Village, Scheeletorget 1, 223 81 Lund, Sweden
- 4Department of Pharmacology, School of Medicine, University of California-San Diego, La Jolla, CA 90095, USA
- 5Harvard Stem Cell Institute, Cambridge, MA 02138, USA
- 6Division of Health Sciences and Technology, Harvard-Massachusetts Institute of Technology, Cambridge, MA 02139, USA
Abstract
Chronic kidney disease (CKD) is a significant global health burden and a leading cause of death in the United States. Chronic inflammation contributes to fibrosis and CKD progression. Here, we present evidence that a key pro-inflammatory group IVA phospholipase A2 enzyme (cPLA2α) is critical to the development of kidney inflammation and fibrosis and can be targeted pharmacologically to attenuate CKD in animal models. Consistent with a role in human disease, overexpression of cPLA2α is seen in kidneys from patients suffering from CKD, and its expression is inversely correlated with the glomerular filtration rate. Genetic ablation of cPLA2α or inhibition with 1-octadeca-3,6,9,12,15-pentaenylsulfanyl-propan-2-one (AVX002) reduced inflammation and ameliorated renal fibrosis in mouse and rat disease models. In addition, reduced levels of eleven arachidonic acid-derived plasma eicosanoids demonstrated inhibitor effectiveness and specificity. Furthermore, AVX002 dose-dependently reduced kidney fibroblast production of profibrotic, pro-inflammatory components leading to progressive fibrotic kidney failure. In conclusion, our results strongly suggest that inhibition of cPLA2α holds promise as a novel therapeutic strategy for renal fibrosis and chronic kidney disease.
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BibTeX
@article{johansen2026group,
title = {{Group IVA Cytosolic Phospholipase A2 (cPLA2α): Pharmacological Inhibition Attenuates Kidney Inflammation and Fibrosis}},
author = {Berit Johansen and Said Movahedi Naini and Linn-Karina Selvik and Astrid Jullumstrø Feuerherm and Felicity J. Ashcroft and Chang Wang and Samuel Mon-Wei Yu and Wenqing Yin and Konstantinos Alevizopoulos and Oswald Quehenberger and Edward A. Dennis and Joseph V. Bonventre},
journal = {Biomolecules},
year = {2026},
month = oct,
doi = {10.3390/biom16101430},
url = {https://www.mdpi.com/2218-273X/16/10/1430},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Group IVA Cytosolic Phospholipase A2 (cPLA2α): Pharmacological Inhibition Attenuates Kidney Inflammation and Fibrosis
AU - Berit Johansen
AU - Said Movahedi Naini
AU - Linn-Karina Selvik
AU - Astrid Jullumstrø Feuerherm
AU - Felicity J. Ashcroft
AU - Chang Wang
AU - Samuel Mon-Wei Yu
AU - Wenqing Yin
AU - Konstantinos Alevizopoulos
AU - Oswald Quehenberger
AU - Edward A. Dennis
AU - Joseph V. Bonventre
PY - 2026
DA - 2026/10/01
JO - Biomolecules
DO - 10.3390/biom16101430
UR - https://www.mdpi.com/2218-273X/16/10/1430
AB - Chronic kidney disease (CKD) is a significant global health burden and a leading cause of death in the United States. Chronic inflammation contributes to fibrosis and CKD progression. Here, we present evidence that a key pro-inflammatory group IVA phospholipase A2 enzyme (cPLA2α) is critical to the development of kidney inflammation and fibrosis and can be targeted pharmacologically to attenuate CKD in animal models. Consistent with a role in human disease, overexpression of cPLA2α is seen in kidneys from patients suffering from CKD, and its expression is inversely correlated with the glomerular filtration rate. Genetic ablation of cPLA2α or inhibition with 1-octadeca-3,6,9,12,15-pentaenylsulfanyl-propan-2-one (AVX002) reduced inflammation and ameliorated renal fibrosis in mouse and rat disease models. In addition, reduced levels of eleven arachidonic acid-derived plasma eicosanoids demonstrated inhibitor effectiveness and specificity. Furthermore, AVX002 dose-dependently reduced kidney fibroblast production of profibrotic, pro-inflammatory components leading to progressive fibrotic kidney failure. In conclusion, our results strongly suggest that inhibition of cPLA2α holds promise as a novel therapeutic strategy for renal fibrosis and chronic kidney disease.
SN - 2218-273X
ER -