{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T09:48:50Z","timestamp":1791884930015,"version":"4.3.4"},"reference-count":42,"publisher":"Wiley","license":[{"start":{"date-parts":[[2022,9,12]],"date-time":"2022-09-12T00:00:00Z","timestamp":1662940800000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Fujian Province Major Science and Technology Program","award":["2018YZ0001-1"],"award-info":[{"award-number":["2018YZ0001-1"]}]},{"name":"Fujian Province Major Science and Technology Program","award":["2019J01683"],"award-info":[{"award-number":["2019J01683"]}]},{"DOI":"10.13039\/501100003392","name":"Natural Science Foundation of Fujian Province","doi-asserted-by":"publisher","award":["2018YZ0001-1"],"award-info":[{"award-number":["2018YZ0001-1"]}],"id":[{"id":"10.13039\/501100003392","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003392","name":"Natural Science Foundation of Fujian Province","doi-asserted-by":"publisher","award":["2019J01683"],"award-info":[{"award-number":["2019J01683"]}],"id":[{"id":"10.13039\/501100003392","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Journal of Immunology Research"],"published-print":{"date-parts":[[2022,9,12]]},"abstract":"<jats:p>Purpose. To investigate the function of C\/EBP\u03b1 in the development of aortic dissection (AD) and the underlying mechanism. Methods. Aortic vascular smooth muscle cells (VSMCs) were isolated, cultured, and identified from AD rats. Then, C\/EBP\u03b1 and PIK3C2A were knockdown or overexpressed by siRNA or plasmid transfection, respectively. Rapamycin or 3-MA was utilized to stimulate and restrain autophagy of VSMCs, respectively. Western blot was used to evaluate the expression levels of C\/EBP\u03b1, PIK3C2A, LC3, Beclin-1, p62, MMP-2, MMP-9, \u03b1-SMA, SM-MHC, and OPN. The pathological status of aortic ring was evaluated by stretch stress, and ChIP assay was used to analyze the binding between C\/EBP\u03b1 and PIK3C2A. C\/EBP\u03b1 shRNA was injected into tail vein to observe the effect of C\/EBP\u03b1 knockdown in vivo on phenotype, autophagy of aortic vascular tissue by immunohistochemical staining and Western blot. Results. The protein levels of C\/EBP\u03b1, PIK3C2A, MMP-2, MMP-9, and LC3 in the aorta of AD rats were all upregulated significantly. C\/EBP\u03b1 and rapamycin promoted notable upregulation of the synthesized proteins (OPN), PIK3C2A, matrix metalloproteinases, LC3, and Beclin-1 in VSMCs, while suppressed contractile proteins (\u03b1-SMA and SM-MHC) and p62. The opposite results were observed in the C\/EBP\u03b1-knockdown VSMCs, PIK3C2A-knockdown VSMCs, or VSMCs treated with 3-MA. C\/EBP\u03b1, PIK3C2A, and LC3 were dramatically upregulated by the stimulation of 3\u2009g and 5\u2009g stretch stress. The downregulated contractile proteins, upregulated synthetic proteins, activated autophagy, and aggravated pathological state in 5\u2009g stretch stress-treated aortic rings were significantly reversed by the knockdown of C\/EBP\u03b1. ChIP results indicated that there was a binding site for C\/EBP\u03b1 in the promoter of PIK3C2A. C\/EBP\u03b1 also downregulated \u03b1-SMA level and upregulated OPN levels in AD rats in vivo. Conclusion. Our data indicated that during the development of AD, C\/EBP\u03b1 regulated the transition of VSMC phenotype and extracellular matrix remodeling by activating autophagy through regulating the transcriptional activity of PIK3C2A promoter.<\/jats:p>","DOI":"10.1155\/2022\/7465353","type":"journal-article","created":{"date-parts":[[2022,9,12]],"date-time":"2022-09-12T23:20:20Z","timestamp":1663024820000},"page":"1-14","source":"Crossref","is-referenced-by-count":10,"title":["C\/EBP\u03b1-Mediated Transcriptional Activation of PIK3C2A Regulates Autophagy, Matrix Metalloproteinase Expression, and Phenotypic of Vascular Smooth Muscle Cells in Aortic Dissection"],"prefix":"10.1155","volume":"2022","author":[{"given":"Heng","family":"Lu","sequence":"first","affiliation":[{"name":"Department of Cardiovascular Surgery, Fujian Medical University Union Hospital, Fuzhou, China"},{"name":"Key Laboratory of Cardio-Thoracic Surgery, Fujian Medical University, Fujian Province University, Fuzhou, 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