{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T23:37:14Z","timestamp":1792798634965,"version":"4.5.0"},"reference-count":59,"publisher":"Oxford University Press (OUP)","issue":"10","license":[{"start":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T00:00:00Z","timestamp":1790812800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82370534"],"award-info":[{"award-number":["82370534"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82670710"],"award-info":[{"award-number":["82670710"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Research Team Project of The First Affiliated Hospital of Bengbu Medical University","award":["BYYFY2022TD002"],"award-info":[{"award-number":["BYYFY2022TD002"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,10,9]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background &amp; Aims<\/jats:title>\n                    <jats:p>Crohn\u2019s disease (CD) features hypertrophied mesenteric adipose tissue (htMAT) where dysfunctional adipocytes promote intestinal inflammation via secreting pro-inflammatory adipokines. Our previous work revealed that pathological extracellular matrix (ECM) remodeling correlates with adipocyte dysfunction in htMAT; but the underlying mechanism remains unknown. This study aimed to determine whether aberrant ECM stiffness drives adipocyte dysfunction and the underlying mechanism.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Clinical mesenteric specimens were examined. A tunable 3D hydrogel system modelled mechanical stress on human adipose explants\/primary adipocytes. Roles of Piezo1 and the mitochondrial permeability transition pore (mPTP) were assessed using Yoda1 (Piezo1 agonist), GsMTx4 (Piezo1 inhibitor), and Alisporivir (mPTP inhibitor). Both the adipocyte-specific Piezo1 knockout mouse model (Adipoq-Cre; Piezo1fl\/fl) and the chronic 2,4,6-trinitrobenzenesulfonic acid (TNBS)\u2011induced colitis mouse model provided in vivo validation.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>CD-htMAT showed excessive collagen deposition, increased tissue stiffness, and adipocyte mechanical stress. Piezo1 was upregulated and correlated with both stiffness and dysfunction. In vitro, stiff matrices activated Piezo1, causing calcium influx, mitochondrial calcium overload, and mPTP opening, leading to mitochondrial dysfunction (impaired dynamics, reduced adenosine triphosphate (ATP), oxidative stress) and a pro-inflammatory adipokine profile. Piezo1 activation on soft matrices mimicked this phenotype, while its inhibition on stiff matrices rescued it. Critically, mPTP blockade mitigated damage induced by Piezo1 activation or high stiffness. In vivo, Piezo1 inhibition, mPTP inhibition, or adipocyte-specific knockout of Piezo1 alleviated mesenteric adipocyte mitochondrial injury, improved function, reduced hyperplasia, and attenuated colitis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>We identified a mechanobiological pathway in which ECM stiffness activates Piezo1 in mesenteric adipocytes. This triggers calcium-mediated mitochondrial dysfunction via opening of the mPTP and results in metabolic-inflammatory alterations. The Piezo1-mPTP axis is a promising therapeutic target for CD.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/ecco-jcc\/jjag169","type":"journal-article","created":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T22:44:01Z","timestamp":1792795441000},"source":"Crossref","is-referenced-by-count":0,"title":["From mechanical stress to mesenteric adipocyte dysfunction in Crohn\u2019s disease: an essential role of Piezo1-mediated mitochondrial calcium overload"],"prefix":"10.1093","volume":"20","author":[{"given":"Lugen","family":"Zuo","sequence":"first","affiliation":[{"name":"Department of Gastrointestinal Surgery, The First Affiliated Hospital of Bengbu Medical University , Bengbu,","place":["China"]},{"name":"Anhui Province Key Laboratory of Basic and Translational Research of Inflammation-related Diseases , Bengbu Medical University, 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Bengbu,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingjing","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Gastrointestinal Surgery, The First Affiliated Hospital of Bengbu Medical University , Bengbu,","place":["China"]},{"name":"Anhui Province Key Laboratory of Basic and Translational Research of Inflammation-related Diseases , Bengbu Medical University, Bengbu,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaohua","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Gastrointestinal Surgery, The First Affiliated Hospital of Bengbu Medical University , Bengbu,","place":["China"]},{"name":"Anhui Province Key Laboratory of Basic and Translational Research of Inflammation-related Diseases , Bengbu Medical University, Bengbu,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bowen","family":"Song","sequence":"additional","affiliation":[{"name":"Department of Gastrointestinal Surgery, The First Affiliated Hospital of Bengbu Medical University , Bengbu,","place":["China"]},{"name":"Anhui Province Key Laboratory of Basic and Translational Research of Inflammation-related Diseases , Bengbu Medical University, Bengbu,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hui","family":"Lu","sequence":"additional","affiliation":[{"name":"Department of Gastrointestinal Surgery, The First Affiliated Hospital of Bengbu Medical University , Bengbu,","place":["China"]},{"name":"Anhui Province Key Laboratory of Basic and Translational Research of Inflammation-related Diseases , Bengbu Medical University, Bengbu,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sitang","family":"Ge","sequence":"additional","affiliation":[{"name":"Department of Gastrointestinal Surgery, The First Affiliated Hospital of Bengbu Medical University , Bengbu,","place":["China"]},{"name":"Anhui Province Key Laboratory of Basic and Translational Research of Inflammation-related Diseases , Bengbu Medical University, Bengbu,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Li","sequence":"additional","affiliation":[{"name":"Anhui Province Key Laboratory of Basic and Translational Research of Inflammation-related Diseases , Bengbu Medical University, Bengbu,","place":["China"]},{"name":"Department of Clinical Laboratory, The First Affiliated Hospital of Bengbu Medical University , Bengbu,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xue","family":"Song","sequence":"additional","affiliation":[{"name":"Anhui Province Key Laboratory of Basic and Translational Research of Inflammation-related Diseases , Bengbu Medical University, Bengbu,","place":["China"]},{"name":"Department of Central Laboratory, The First Affiliated Hospital of Bengbu Medical University , Bengbu,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yueyue","family":"Wang","sequence":"additional","affiliation":[{"name":"Anhui Province Key Laboratory of Basic and Translational Research of Inflammation-related Diseases , Bengbu Medical University, Bengbu,","place":["China"]},{"name":"Department of Clinical Laboratory, The First Affiliated Hospital of Bengbu Medical University , 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