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Here, we investigated the protective effects and the regulatory mechanism of protocatechuic acid, a phenolic compound, using a mouse model of isoproterenol-induced cardiac hypertrophy. Our results demonstrated that protocatechuic acid treatment significantly downregulated the expression of cardiac hypertrophic markers (<jats:italic>Nppa, Nppb<\/jats:italic>, and <jats:italic>Myh7<\/jats:italic>), cardiomyocyte size, heart weight to body weight ratio, cross-sectional area, and thickness of left ventricular septum and posterior wall. This treatment also reduced the expression of isoproterenol-induced ROCK1, Sp1, and PKC\u03b3 both in vivo and in vitro. To investigate the mechanism, we performed knockdown and overexpression experiments. The knockdown of ROCK1, Sp1, or PKC\u03b3 decreased the isoproterenol-induced cell area and the expression of hypertrophic markers, while the overexpression of Sp1 or PKC\u03b3 increased the levels of hypertrophic markers. Protocatechuic acid treatment reversed these effects. Interestingly, the overexpression of Sp1 increased cell area and induced PKC\u03b3 expression. Furthermore, experiments using transcription inhibitor actinomycin D showed that ROCK1 and Sp1 suppression by protocatechuic acid was not regulated at the transcriptional level. Our results indicate that protocatechuic acid acts via the ROCK1\/Sp1\/PKC\u03b3 axis and therefore has promising therapeutic potential as a treatment for cardiac hypertrophy.<\/jats:p>","DOI":"10.1038\/s41598-021-96761-2","type":"journal-article","created":{"date-parts":[[2021,8,30]],"date-time":"2021-08-30T10:02:57Z","timestamp":1630317777000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":31,"title":["Protocatechuic acid attenuates isoproterenol-induced cardiac hypertrophy via downregulation of ROCK1\u2013Sp1\u2013PKC\u03b3 axis"],"prefix":"10.1038","volume":"11","author":[{"given":"Liyan","family":"Bai","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hae Jin","family":"Kee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiongyi","family":"Han","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tingwei","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seung-Jung","family":"Kee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Myung Ho","family":"Jeong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,8,30]]},"reference":[{"key":"96761_CR1","doi-asserted-by":"publisher","first-page":"1580","DOI":"10.1161\/01.CIR.0000120390.68287.BB","volume":"109","author":"N Frey","year":"2004","unstructured":"Frey, N., Katus, H. 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