Browsing by Subject "Extracellular signalling molecules"

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    MiR-150 blunts cardiac dysfunction in mice with cardiomyocyte loss of β1-adrenergic receptor/β-arrestin signaling and controls a unique transcriptome
    (Springer Nature, 2022-12-30) Moukette, Bruno; Kawaguchi, Satoshi; Sepulveda, Marisa N.; Hayasaka, Taiki; Aonuma, Tatsuya; Liangpunsakul, Suthat; Yang, Lei; Dharmakumar, Rohan; Conway, Simon J.; Kim, Il-man; Anatomy, Cell Biology and Physiology, School of Medicine
    The β1-adrenergic receptor (β1AR) is found primarily in hearts (mainly in cardiomyocytes [CMs]) and β-arrestin-mediated β1AR signaling elicits cardioprotection through CM survival. We showed that microRNA-150 (miR-150) is upregulated by β-arrestin-mediated β1AR signaling and that CM miR-150 inhibits maladaptive remodeling post-myocardial infarction. Here, we investigate whether miR-150 rescues cardiac dysfunction in mice bearing CM-specific abrogation of β-arrestin-mediated β1AR signaling. Using CM-specific transgenic (TG) mice expressing a mutant β1AR (G protein-coupled receptor kinase [GRK]–β1AR that exhibits impairment in β-arrestin-mediated β1AR signaling), we first generate a novel double TG mouse line overexpressing miR-150. We demonstrate that miR-150 is sufficient to improve cardiac dysfunction in CM-specific GRK–β1AR TG mice following chronic catecholamine stimulation. Our genome-wide circular RNA, long noncoding RNA (lncRNA), and mRNA profiling analyses unveil a subset of cardiac ncRNAs and genes as heretofore unrecognized mechanisms for beneficial actions of β1AR/β-arrestin signaling or miR-150. We further show that lncRNA Gm41664 and GDAP1L1 are direct novel upstream and downstream regulators of miR-150. Lastly, CM protective actions of miR-150 are attributed to repressing pro-apoptotic GDAP1L1 and are mitigated by pro-apoptotic Gm41664. Our findings support the idea that miR-150 contributes significantly to β1AR/β-arrestin-mediated cardioprotection by regulating unique ncRNA and gene signatures in CMs.
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    Neurotensin-neurotensin receptor 2 signaling in adipocytes suppresses food intake through regulating ceramide metabolism
    (Springer Nature, 2025) Fu, Wei; Lai, Yuanting; Li, Kexin; Yang, Yue; Guo, Xiao; Gong, Qifan; Zhou, Xiaofeng; Zhou, Liying; Liu, Cenxi; Zhang, Zhi; So, Jisun; Zhang, Yufeng; Huang, Lin; Lu, Guangxing; Yi, Chuanyou; Wang, Qichu; Fan, Chenyu; Liu, Chao; Wang, Jiaxing; Yu, Haiyi; Zhao, Yimin; Huang, Tao; Roh, Hyun Cheol; Liu, Tiemin; Tang, Huiru; Qi, Jianping; Xu, Ming; Zheng, Yan; Huang, He; Li, Jin; Biochemistry and Molecular Biology, School of Medicine
    Neurotensin (NTS) is a secretory peptide produced by lymphatic endothelial cells. Our previous study revealed that NTS suppressed the activity of brown adipose tissue via interactions with NTSR2. In the current study, we found that the depletion of Ntsr2 in white adipocytes upregulated food intake, while the local treatment of NTS suppressed food intake. Our mechanistic study revealed that suppression of NTS-NTSR2 signaling enhanced the phosphorylation of ceramide synthetase 2, increased the abundance of its products ceramides C20-C24, and downregulated the production of GDF15 in white adipose tissues, which was responsible for the elevation of food intake. We discovered a potential causal and positive correlation between serum C20-C24 ceramide levels and human food intake in four populations with different ages and ethnic backgrounds. Together, our study shows that NTS-NTSR2 signaling in white adipocytes can regulate food intake via its direct control of lipid metabolism and production of GDF15. The ceramides C20-C24 are key factors regulating food intake in mammals.