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RETRACTED ARTICLE: Silencing of CREB Inhibits HDAC2/TLR4/NF-κB Cascade to Relieve Severe Acute Pancreatitis-Induced Myocardial Injury

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Abstract

The purpose of the present study is to investigate the role of CREB in cardiomyocytes proliferation in regulation of HDAC2-dependent TLR4/NF-κB pathway in severe acute pancreatitis (SAP)-induced myocardial injury. The SAP rat model was developed by injecting sodium touracholate into SD rats and then infected with lentivirus vectors expressing sh-CREB in the presence/absence of LPS. The pathological alterations of rat pancreatic and cardiac tissues were observed by HE staining. TUNEL assay was used to study apoptosis of cardiomyocytes. Next, the loss- and gain-function assay was conducted in LPS-induced myocardial injury cardiomyocytes to define the roles of CREB, HDAC2, and TLR4 in cardiomyocyte proliferation, apoptosis, inflammation, and myocardial injury in vitro. ChIP assay was used to study the enrichment of CREB bound to HDAC2 promoter. RT-qPCR and Western blot analysis were used to detect the expressions of related mRNA and proteins in the NF-κB pathway, respectively. CREB was found to be overexpressed in both SAP tissues and cells. CREB directly bound to the promoter of HDAC2 and activated its expression. Overexpressed CREB or HDAC2 inhibited proliferation and promoted apoptosis of cardiomyocytes. Suppression of CREB inhibited the HDAC2/TLR4/NF-κB cascade to promote proliferation and inhibit apoptosis of cardiomyocytes. The in vitro results were validated in vivo experiments. Coherently, suppression of CREB can inhibit HDAC2/TLR4/NF-κB cascade to promote cardiomyocyte proliferation, thus ameliorating SAP-induced myocardial injury.

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Data Availability

The data sets used and/or analyzed during the current study are available from the corresponding author on reasonable request.

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Acknowledgements

We would like to acknowledge the reviewers for their helpful comments on this paper.

Funding

This work was supported by Scientific Research Fund Project of Shaanxi Provincial Health and Family Planning Commission (No. 2016D015), Science and Technology Planning Project of Xi’an (No. 2017113SF/YX007(15)), and Shaanxi Provincial Science and Technology Research Subject of Traditional Chinese Medicine (No. 2019-ZZ-JC031).

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  1. Department of Emergency, the Second Affiliated Hospital of Xi’an Jiaotong University, No. 157 Xiwu Road, Xincheng District, 710004, Xi’an, Shaanxi Province, People’s Republic of China

    Longfei Pan, Zequn Niu, Yanxia Gao, Liming Wang, Zhong Liu, Jie Liu, Jiangli Sun & Honghong Pei

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  1. Longfei Pan
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  2. Zequn Niu
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Contributions

(I) Conception and design: Longfei Pan, Zequn Niu, Yanxia Gao; (II) administrative support: Yanxia Gao, Liming Wang, Zhong Liu, Jie Liu; (III) provision of study materials: Jiangli Sun, Honghong Pei; (IV) collection and assembly of data: Longfei Pan, Zequn Niu, Yanxia Gao; (V) data analysis and interpretation: Longfei Pan, Zequn Niu, Jiangli Sun; (VI) manuscript writing: Zequn Niu, Yanxia Gao; (VII) final approval of manuscript: all authors.

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Correspondence to Longfei Pan.

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The study and procedures were complied with the Laboratory Animal Care and Use Guide (NIH Publication NO. 85-23, revised 2011). Animal study was approved by the laboratory animal care committee of Xi’an Jiaotong University.

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Pan, L., Niu, Z., Gao, Y. et al. RETRACTED ARTICLE: Silencing of CREB Inhibits HDAC2/TLR4/NF-κB Cascade to Relieve Severe Acute Pancreatitis-Induced Myocardial Injury. Inflammation 44, 1565–1580 (2021). https://doi.org/10.1007/s10753-021-01441-y

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