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

• Published in: Clinical and experimental medicine 2023-11, Vol.23 (7), p.3589-3603
• Main Authors: Peng, Kang, Biao, Chen, Zhao, Yin Yong, Jun, Li Chao, Wei, Wang, A Bu Li Zi, Yi Li Ni Ya Zi, Song, Lin
• Format: Article
• Language: English
• Subjects: Animal models; Dephosphorylation; Hematology; Homology; Inflammation; Internal Medicine; Lipopolysaccharides; Macrophages; Medicine; Medicine & Public Health; Non-coding RNA; Oncology; Pancreatitis; Polarization; Polymerase chain reaction; Protein-tyrosine-phosphatase; Sodium; Stat3 protein
• ISSN: 1591-9528; 1591-8890; 1591-9528
• DOI: 10.1007/s10238-023-01126-w

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.