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Long non-coding RNA MM2P suppresses M1-polarized macrophages-mediated excessive inflammation to prevent sodium taurocholate-induced acute pancreatitis by blocking SHP2-mediated STAT3 dephosphorylation

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Abstract

M1 macrophage-mediated excessive inflammatory response plays a key role in the onset and progression of acute pancreatitis (AP), and this study aimed to investigate the role and underlying mechanisms by which the macrophage polarization-related long noncoding RNA (lncRNA) MM2P participated in the regulation of AP progression. By performing quantitative reverse-transcription PCR (qRT-PCR) assay, lncRNA MM2P was found to be downregulated in both sodium taurocholate-induced AP model mice tissues and lipopolysaccharide (LPS)-stimulated RAW264.7 cells, and gain-of-function experiments confirmed that overexpression of lncRNA MM2P counteracted inflammatory responses, reduced macrophage infiltration and facilitated M1-to-M2 transformation of macrophages to ameliorate AP development in vitro and in vivo. Further mechanical experiments revealed that lncRNA MM2P inhibited Src homology 2 containing protein tyrosine phosphatase 2 (SHP2)-mediated signal transducer and activator of transcription 3 (STAT3) dephosphorylation to activate the STAT3 signaling, and silencing of SHP2 suppressed M1 type skewing in LPS-induced RAW264.7 cells. Interestingly, our rescuing experiments verified that lncRNA MM2P-induced suppressing effects on M1-polarization of LPS-treated RAW264.7 cells were abrogated by co-treating cells with STAT3 inhibitor stattic. Collectively, our data for the first time revealed that lncRNA MM2P suppressed M1-polarized macrophages to attenuate the progression of sodium taurocholate-induced AP, and lncRNA MM2P might be an ideal biomarker for AP diagnosis and treatment.

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The data were all included in this paper. The original data are available from the corresponding author upon reasonable request.

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Authors and Affiliations

  1. General Surgery Department, The First People’s Hospital of Urumqi, Urumqi, 830011, China

    Kang Peng, Chen Biao, Yin Yong Zhao, Li Chao Jun, Wang Wei & Yi Li Ni Ya Zi A Bu Li Zi

  2. General Surgery Department, The First People’s Hospital of Urumqi (Children’s Hospital of Urumqi), Jiankang Road No. 1, Tianshan District, Urumqi, 830002, Xinjiang, China

    Lin Song

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  1. Kang Peng
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Contributions

KP and CB conceived and designed the experiments, LCJ, WW and YYZ performed the experiments and analyzed the data, LS, CB and YYZ draft the manuscript, LS, KP and YLNYZ·ABLZ revised the manuscript. All authors reviewed the manuscript.

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Correspondence to Lin Song.

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Peng, K., Biao, C., Zhao, Y.Y. et al. Long non-coding RNA MM2P suppresses M1-polarized macrophages-mediated excessive inflammation to prevent sodium taurocholate-induced acute pancreatitis by blocking SHP2-mediated STAT3 dephosphorylation. Clin Exp Med 23, 3589–3603 (2023). https://doi.org/10.1007/s10238-023-01126-w

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