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Glutamine-rich protein 1 (QRICH1), as a transcriptional regulator, belongs to the caspase recruitment domain (CARD)-containing gene family. QRICH1 has been shown to influence the outcomes of endoplasmic reticulum stress by regulating the transcription of proteostasis-related genes. In this study, we explored the role of QRICH1 in pathological cardiac hypertrophy.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Methods<\/jats:title>\n            <jats:p>We observed an increased expression of QRICH1 in the hearts of humans and mice with left ventricular hypertrophy (LVH). To assess the functional impact in this context, we employed gain- and loss-of-function approaches, using AAV9 injections to establish cardiac-specific QRICH1 knockdown or overexpression models in transverse aortic constriction (TAC) or isoproterenol (ISO)-induced cardiac hypertrophy.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Results<\/jats:title>\n            <jats:p>Our data indicated that cardiomyocyte-specific knockdown of QRICH1 alleviated the hypertrophic phenotype in response to TAC or ISO injection. However, overexpression of QRICH1 exacerbated cardiac hypertrophy, remodeling, dysfunction, cell apoptosis, and inflammatory responses. Mechanistically, we demonstrated that ATF6 was significantly enriched by QRICH1 in cardiomyocytes treated with ISO using RNA-seq combined with CUT&amp;TAG analysis. ChIP-qPCR and luciferase assays further confirmed that ATF6 is a target gene of QRICH1 in cardiomyocytes under growth stimulation. Knockdown of QRICH1 in cardiomyocytes blocked ISO-mediated induction of ATF6, activation of mTORC1, and cellular growth. And all of the above was restored by the overexpression of ATF6.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions<\/jats:title>\n            <jats:p>QRICH1 plays a pivotal role in cardiac hypertrophy by regulating ATF6, and QRICH1 may be a potential new therapeutic target for pathological cardiac hypertrophy.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1186\/s10020-025-01241-2","type":"journal-article","created":{"date-parts":[[2025,5,13]],"date-time":"2025-05-13T00:54:01Z","timestamp":1747097641000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["QRICH1 regulates ATF6 transcription to affect pathological cardiac hypertrophy progression"],"prefix":"10.1186","volume":"31","author":[{"given":"Lihui","family":"Zhang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongping","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guangmei","family":"Zou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenjuan","family":"Jia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haibin","family":"Dong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chunxiao","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hua","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yugang","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Da","family":"Teng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bowen","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lin","family":"Zhong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lei","family":"Gong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,5,13]]},"reference":[{"key":"1241_CR1","doi-asserted-by":"publisher","first-page":"783","DOI":"10.1038\/s41569-022-00718-5","volume":"19","author":"I Akoumianakis","year":"2022","unstructured":"Akoumianakis I, Polkinghorne M, Antoniades C. 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