{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T22:18:33Z","timestamp":1789510713528,"version":"build-2803163510"},"reference-count":63,"publisher":"American Society for Clinical Investigation","issue":"19","license":[{"start":{"date-parts":[[2022,10,10]],"date-time":"2022-10-10T00:00:00Z","timestamp":1665360000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"NIH - NHLBI","award":["R35 HL-135827"],"award-info":[{"award-number":["R35 HL-135827"]}]},{"DOI":"10.13039\/100000968","name":"American Heart Association","doi-asserted-by":"crossref","award":["20POST35180102"],"award-info":[{"award-number":["20POST35180102"]}],"id":[{"id":"10.13039\/100000968","id-type":"DOI","asserted-by":"crossref"}]},{"name":"NIH-NHLBI","award":["1K99HL155840"],"award-info":[{"award-number":["1K99HL155840"]}]},{"name":"Boehringer Ingelheim","award":["BI-JHU Grant for TRPC6 in DMD"],"award-info":[{"award-number":["BI-JHU Grant for TRPC6 in DMD"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2022,10,10]]},"abstract":"<jats:p>\n                    Gene mutations causing loss of dystrophin result in the severe muscle disease known as Duchenne muscular dystrophy (DMD). Despite efforts at genetic repair, DMD therapy remains largely palliative. Loss of dystrophin destabilizes the sarcolemmal membrane, inducing mechanosensitive cation channels to increase calcium entry and promote cell damage and, eventually, muscle dysfunction. One putative channel is transient receptor potential canonical 6 (TRPC6); we have shown that TRPC6 contributed to abnormal force and calcium stress-responses in cardiomyocytes from mice lacking dystrophin that were haplodeficient for utrophin (\n                    <jats:italic>\n                      mdx\/utrn\n                      <jats:sup>+\/\u2013<\/jats:sup>\n                    <\/jats:italic>\n                    [HET] mice). Here, we show in both the HET mouse and the far more severe homozygous\n                    <jats:italic>\n                      mdx\/utrn\n                      <jats:sup>\u2013\/\u2013<\/jats:sup>\n                    <\/jats:italic>\n                    mouse that TRPC6 gene deletion or its selective pharmacologic inhibition (by BI 749327) prolonged survival 2- to 3-fold, improving skeletal and cardiac muscle and bone defects. Gene pathways reduced by BI 749327 treatment most prominently regulated fat metabolism and TGF-\u03b21 signaling. These results support the testing of TRPC6 inhibitors in human trials for other diseases as a novel DMD therapy.\n                  <\/jats:p>","DOI":"10.1172\/jci.insight.158906","type":"journal-article","created":{"date-parts":[[2022,9,13]],"date-time":"2022-09-13T12:01:02Z","timestamp":1663070462000},"source":"Crossref","is-referenced-by-count":25,"title":["Pharmacological TRPC6 inhibition improves survival and muscle function in mice with Duchenne muscular dystrophy"],"prefix":"10.1172","volume":"7","author":[{"given":"Brian L.","family":"Lin","sequence":"first","affiliation":[{"name":"Department of Cardiology,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joseph Y.","family":"Shin","sequence":"additional","affiliation":[{"name":"Department of Cardiology,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William P.D.","family":"Jeffreys","sequence":"additional","affiliation":[{"name":"Department of 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