{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T06:04:42Z","timestamp":1790661882696,"version":"4.1.0"},"reference-count":34,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T00:00:00Z","timestamp":1790640000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81860346"],"award-info":[{"award-number":["81860346"]}],"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":["81560318"],"award-info":[{"award-number":["81560318"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012543","name":"Youth Science Foundation of Guangxi Medical University","doi-asserted-by":"publisher","award":["GXMUYSF202316"],"award-info":[{"award-number":["GXMUYSF202316"]}],"id":[{"id":"10.13039\/501100012543","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cell Dev. Biol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      Myocardial ischemia\/reperfusion (MI\/R) injury involves oxidative stress, lysosomal dysfunction, and altered autophagy. TRPV4 may link Ca\n                      <jats:sup>2+<\/jats:sup>\n                      dysregulation to these processes, but its role in lysosomal membrane permeabilization (LMP) and autophagic impairment remains unclear.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Three disease-matched mouse-heart GEO cohorts (GSE281940, GSE130217, and GSE160516) were analyzed using limma-based differential expression, prespecified oxidative, lysosomal, and autophagy-related gene sets, cross-cohort comparisons, and within-cohort correlations. H9C2 cardiomyoblasts subjected to OGD\/R were used to examine intracellular Ca\n                      <jats:sup>2+<\/jats:sup>\n                      , ROS, LMP, autophagy-related changes, inflammatory cytokine release, and cell injury after pharmacological modulation of TRPV4 and ROS.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      All three cohorts showed clear MI\/R-associated transcriptional changes. Hmox1 was consistently increased across all five prespecified contrasts, whereas\n                      <jats:italic>Trpv4<\/jats:italic>\n                      showed modest, time-dependent changes without reaching FDR-adjusted significance.\n                      <jats:italic>Trpv4<\/jats:italic>\n                      was positively correlated with\n                      <jats:italic>Map1lc3b<\/jats:italic>\n                      in all three cohorts (Spearman \u03c1 = 0.73\u20130.83, nominal P &amp;lt; 0.05), while associations with oxidative and lysosomal genes were more variable. In H9C2 cardiomyoblasts, OGD\/R increased TRPV4 mRNA expression, intracellular Ca\n                      <jats:sup>2+<\/jats:sup>\n                      , and ROS levels. TRPV4 inhibition reduced ROS accumulation, attenuated LMP-related changes, and decreased LC3B and p62 accumulation, whereas TRPV4 activation produced the opposite effects. NAC attenuated TRPV4 activation-induced ROS and lysosomal injury, while t-BHP partially reversed the effects of TRPV4 inhibition. OGD\/R also increased IL-1\u03b2, IL-6, and TNF-\u03b1 release, which was reduced by TRPV4 inhibition.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>The transcriptomic data indicate a context-dependent TRPV4 response within a conserved MI\/R stress background. The H9C2 cardiomyoblasts experiments support the involvement of the TRPV4\u2013ROS\u2013LMP pathway in lysosomal injury, impaired autophagic degradation, inflammatory responses, and OGD\/R-induced cardiomyoblast injury.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fcell.2026.1945533","type":"journal-article","created":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T05:50:56Z","timestamp":1790661056000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["TRPV4-linked oxidative\u2013lysosomal stress in myocardial ischemia\/reperfusion: disease-matched transcriptomics and functional analysis in OGD\/R cardiomyoblasts"],"prefix":"10.3389","volume":"14","author":[{"given":"Jie","family":"Yang","sequence":"first","affiliation":[{"name":"Department of Emergency, The First Affiliated Hospital of Guangxi Medical University","place":["Nanning, Guangxi, 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