Prolactin-Releasing Peptide Differentially Regulates Gene Transcriptomic Profiles in Mouse Bone Marrow-Derived Macrophages

Abstract

Prolactin-releasing Peptide (PrRP) is a neuropeptide whose receptor is GPR10. Recently, the regulatory role of PrRP in the neuroendocrine field has attracted increasing attention. However, the influence of PrRP on macrophages, the critical housekeeper in the neuroendocrine field, has not yet been fully elucidated. Here, we investigated the effect of PrRP on the transcriptome of mouse bone marrow-derived macrophages (BMDMs) with RNA sequencing, bioinformatics, and molecular simulation. BMDMs were exposed to PrRP (18 h) and were subjected to RNA sequencing. Differentially expressed genes (DEGs) were acquired, followed by GO, KEGG, and PPI analysis. Eight qPCR-validated DEGs were chosen as hub genes. Next, the three-dimensional structures of the proteins encoded by these hub genes were modeled by Rosetta and Modeller, followed by molecular dynamics simulation by the Gromacs program. Finally, the binding modes between PrRP and hub proteins were investigated with the Rosetta program. PrRP showed no noticeable effect on the morphology of macrophages. A total of 410 DEGs were acquired, and PrRP regulated multiple BMDM-mediated functional pathways. Besides, the possible docking modes between PrRP and hub proteins were investigated. Moreover, GPR10 was expressed on the cell membrane of BMDMs, which increased after PrRP exposure. Collectively, PrRP significantly changed the transcriptome profile of BMDMs, implying that PrRP may be involved in various physiological activities mastered by macrophages.

An analogue of the Prolactin Releasing Peptide reduces obesity and promotes adult neurogenesis

“…The role of LiPR in regulating cell cycle is also supported by our findings that it reduces proliferation both in the MBH and the SGZ and influences the expression of genes that control the cell cycle (e.g. Cdk8, Jarid2) (Adhikari et al, 2019 ; Alarcon et al, 2009 ) Interestingly, recent RNAseq data from mouse macrophages exposed to PrRP for only 18 h reveal DEGs related not only to neuronal differentiation but also to cell cycle or inflammation, such as Cdkn2a or Il1b (Sun et al, 2021 ). In addition, we show that HFD+LiPR also increases the proportion of Vimentin+GFAP+ tanycytes, a subset of α-tanycytes (Goodman and Hajihosseini, 2015 ), which may be protective against HFD-induced changes as Vimentin is responsive to HFD (Kim et al, 2021 ) and is downregulated in tanycytes of mice with a hypermetabolic phenotype (Holmes et al, 2016 ).…”

An analogue of the Prolactin Releasing Peptide reduces obesity and promotes adult neurogenesis

“…81,82 Interestingly, recent RNAseq data from mouse macrophages exposed to PrRP for only 18 hours reveal DEGs related not only to neuronal differentiation but also to cell cycle or inflammation, such as Cdkn2a or Il1b. 83 In addition, we show that HFD+LiPR also increases the proportion of Vimentin+GFAP+ tanycytes, a subset of α-tanycytes 84 , which may be protective against HFD-induced changes as Vimentin is responsive to HFD 52 and is downregulated in tanycytes of mice with a hypermetabolic phenotype. 54 Taken together, our results improve our understanding of how the HFD and the anti-obesity pharmacology influence tanycytes, which act not only as htNSCs but as metabolic regulators that control vascular permeability, leptin transport 85 and the entry of anti-obesity compounds such as Liraglutide to the hypothalamic parenchyma.…”

Transcriptomics Changes in the Peritoneum of Mice with Lipopolysaccharide-Induced Peritonitis

“…RNA sequencing was performed as previously described [ 45 , 46 , 47 ]. RNA integrity was detected by using the RNA Nano 6000 Assay Kit (Agilent Technologies, Santa Clara, CA, USA).…”