{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,29]],"date-time":"2026-10-29T06:11:13Z","timestamp":1793254273975,"version":"4.5.0"},"reference-count":70,"publisher":"National Academy of Sciences","issue":"40","license":[{"start":{"date-parts":[[2025,10,2]],"date-time":"2025-10-02T00:00:00Z","timestamp":1759363200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000050","name":"HHS | NIH | National Heart, Lung, and Blood Institute","doi-asserted-by":"publisher","award":["R01HL151735"],"award-info":[{"award-number":["R01HL151735"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000057","name":"HHS | NIH | National Institute of General Medical Sciences","doi-asserted-by":"publisher","award":["R35GM149218"],"award-info":[{"award-number":["R35GM149218"]}],"id":[{"id":"10.13039\/100000057","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000057","name":"HHS | NIH | National Institute of General Medical Sciences","doi-asserted-by":"publisher","award":["R35GM153208"],"award-info":[{"award-number":["R35GM153208"]}],"id":[{"id":"10.13039\/100000057","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2025,10,7]]},"abstract":"<jats:p>\n                    Sickle cell disease (SCD), an inherited blood disorder caused by a mutation in the \u03b2-globin gene, is characterized by sickle erythrocytes that are prone to hemolysis, leading to anemia and vaso-occlusion crises. In sickle erythrocytes, hemoglobin aggregation is followed by altered cation permeability and subsequent dehydration. Interventions that restore cation permeability can decrease hemolysis and ameliorate the symptoms associated with SCD. PIEZO1 is a nonselective mechanosensitive cation channel that regulates erythrocyte volume. Gain-of-function (GOF) mutations in PIEZO1 cause hemolytic anemia by increasing cation permeability, leading to erythrocyte dehydration in humans and mice. Although PIEZO1 plays a key role in erythrocyte homeostasis, its role in SCD remains unknown. Here, we demonstrate that the function of the PIEZO1 channel is upregulated in sickle erythrocytes of humans and mice, and this enhancement can be restored through a dietary intervention. We found that PIEZO1 activity in sickle erythrocytes resembles that of the GOF mutation causing hemolytic anemia. A diet enriched in the\n                    <jats:italic toggle=\"yes\">\u03c9<\/jats:italic>\n                    -3 fatty acid eicosapentaenoic (EPA) acid decreases PIEZO1 activity in sickle erythrocytes, attenuates hemolysis, and reduces hypoxia-induced sickling. Furthermore, EPA reduces inflammatory markers. We propose that PIEZO1 contributes to the increase in nonselective cationic conductance (i.e., Psickle), which leads to dehydration downstream of hemoglobin polymerization. Our results suggest that reducing PIEZO1 function represents a promising therapeutic strategy to reestablishing normal cation permeability in SCD.\n                  <\/jats:p>","DOI":"10.1073\/pnas.2514863122","type":"journal-article","created":{"date-parts":[[2025,10,2]],"date-time":"2025-10-02T18:11:50Z","timestamp":1759428710000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":13,"title":["Enhanced PIEZO1 function contributes to the pathogenesis of sickle cell disease"],"prefix":"10.1073","volume":"122","author":[{"given":"Luis O.","family":"Romero","sequence":"first","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, Center for Membrane Biology, McGovern Medical School, University of Texas Health Science Center at Houston","place":["Houston"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-8463-6501","authenticated-orcid":false,"given":"Manisha","family":"Bade","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, Center for Membrane Biology, McGovern Medical School, University of Texas Health Science Center at Houston","place":["Houston"]},{"name":"MD Anderson Cancer Center and University of Texas Health Science Center Graduate School of Biomedical Sciences","place":["Houston"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laila","family":"Elsherif","sequence":"additional","affiliation":[{"name":"Division of Hematology, Center for Sickle Cell Disease, University of Tennessee Health Sciences Center","place":["Memphis"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1991-4844","authenticated-orcid":false,"given":"Jada D.","family":"Williams","sequence":"additional","affiliation":[{"name":"Department of Physiology, University of Tennessee Health Science Center","place":["Memphis"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiangmei","family":"Kong","sequence":"additional","affiliation":[{"name":"Children\u2019s Medical Center Research Institute, Department of Pediatrics, University of Texas Southwestern Medical Center","place":["Dallas"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adebowale","family":"Adebiyi","sequence":"additional","affiliation":[{"name":"Department of Medical Pharmacology and Physiology, University of Missouri","place":["Columbia"]},{"name":"Department of Anesthesiology and Perioperative Medicine, University of Missouri","place":["Columbia"]},{"name":"NextGen Precision Health, University of Missouri","place":["Columbia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kenneth I.","family":"Ataga","sequence":"additional","affiliation":[{"name":"Division of Hematology, Center for Sickle Cell Disease, University of Tennessee Health Sciences Center","place":["Memphis"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3808-0651","authenticated-orcid":false,"given":"Shang","family":"Ma","sequence":"additional","affiliation":[{"name":"Children\u2019s Medical Center Research Institute, Department of Pediatrics, University of Texas Southwestern Medical Center","place":["Dallas"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julio F.","family":"Cordero-Morales","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, Center for Membrane Biology, McGovern Medical School, University of Texas Health Science Center at Houston","place":["Houston"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8494-1534","authenticated-orcid":false,"given":"Valeria","family":"V\u00e1squez","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, Center for Membrane Biology, McGovern Medical School, University of Texas Health Science Center at Houston","place":["Houston"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2025,10,2]]},"reference":[{"key":"e_1_3_4_1_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrdp.2018.10"},{"key":"e_1_3_4_2_2","unstructured":"C. f. 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