PMID- 34065092 OWN - NLM STAT- MEDLINE DCOM- 20210830 LR - 20210830 IS - 2073-4425 (Electronic) IS - 2073-4425 (Linking) VI - 12 IP - 5 DP - 2021 May 9 TI - Transcriptomic Changes in Mouse Bone Marrow-Derived Macrophages Exposed to Neuropeptide FF. LID - 10.3390/genes12050705 [doi] LID - 705 AB - Neuropeptide FF (NPFF) is a neuropeptide that regulates various biological activities. Currently, the regulation of NPFF on the immune system is an emerging field. However, the influence of NPFF on the transcriptome of primary macrophages has not been fully elucidated. In this study, the effect of NPFF on the transcriptome of mouse bone marrow-derived macrophages (BMDMs) was explored by RNA sequencing, bioinformatics, and molecular simulation. BMDMs were treated with 1 nM NPFF for 18 h, followed by RNA sequencing. Differentially expressed genes (DEGs) were obtained, followed by GO, KEGG, and PPI analysis. A total of eight qPCR-validated DEGs were selected as hub genes. Subsequently, the three-dimensional (3-D) structures of the eight hub proteins were constructed by Modeller and Rosetta. Next, the molecular dynamics (MD)-optimized 3-D structure of hub protein was acquired with Gromacs. Finally, the binding modes between NPFF and hub proteins were studied by Rosetta. A total of 2655 DEGs were obtained (up-regulated 1442 vs. down-regulated 1213), and enrichment analysis showed that NPFF extensively regulates multiple functional pathways mediated by BMDMs. Moreover, the 3-D structure of the hub protein was obtained after MD-optimization. Finally, the docking modes of NPFF-hub proteins were predicted. Besides, NPFFR2 was expressed on the cell membrane of BMDMs, and NPFF 1 nM significantly activated NPFFR2 protein expression. In summary, instead of significantly inhibiting the expression of the immune-related gene transcriptome of RAW 264.7 cells, NPFF simultaneously up-regulated and down-regulated the gene expression profile of a large number of BMDMs, hinting that NPFF may profoundly affect a variety of cellular processes dominated by BMDMs. Our work provides transcriptomics clues for exploring the influence of NPFF on the physiological functions of BMDMs. FAU - Sun, Yulong AU - Sun Y AUID- ORCID: 0000-0002-6811-5926 AD - School of Life Sciences, Northwestern Polytechnical University, Xi'an 710072, China. AD - Key Laboratory for Space Biosciences & Biotechnology, Institute of Special Environmental Biophysics, School of Life Sciences, Northwestern Polytechnical University, Xi'an 710072, China. FAU - Kuang, Yuanyuan AU - Kuang Y AD - School of Life Sciences, Northwestern Polytechnical University, Xi'an 710072, China. AD - Key Laboratory for Space Biosciences & Biotechnology, Institute of Special Environmental Biophysics, School of Life Sciences, Northwestern Polytechnical University, Xi'an 710072, China. FAU - Zuo, Zhuo AU - Zuo Z AD - School of Life Sciences, Northwestern Polytechnical University, Xi'an 710072, China. AD - Key Laboratory for Space Biosciences & Biotechnology, Institute of Special Environmental Biophysics, School of Life Sciences, Northwestern Polytechnical University, Xi'an 710072, China. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20210509 PL - Switzerland TA - Genes (Basel) JT - Genes JID - 101551097 RN - 0 (Oligopeptides) RN - 0 (Receptors, Neuropeptide) RN - 0 (neuropeptide FF receptor) RN - 99566-27-5 (phenylalanyl-leucyl-phenylalanyl-glutaminyl-prolyl-glutaminyl-arginyl-phenylalaninamide) SB - IM MH - Animals MH - Binding Sites MH - Cells, Cultured MH - Macrophages/drug effects/*metabolism MH - Mice MH - Mice, Inbred C57BL MH - Oligopeptides/*metabolism/pharmacology MH - Protein Binding MH - Receptors, Neuropeptide/chemistry/genetics/metabolism MH - *Transcriptome PMC - PMC8151073 OTO - NOTNLM OT - RNA sequencing OT - bioinformatics OT - bone marrow-derived macrophage OT - neuropeptide OT - transcriptomic profiles COIS- The authors declare that there is no conflict of interest. EDAT- 2021/06/03 06:00 MHDA- 2021/08/31 06:00 PMCR- 2021/05/09 CRDT- 2021/06/02 01:11 PHST- 2021/03/05 00:00 [received] PHST- 2021/04/28 00:00 [revised] PHST- 2021/05/04 00:00 [accepted] PHST- 2021/06/02 01:11 [entrez] PHST- 2021/06/03 06:00 [pubmed] PHST- 2021/08/31 06:00 [medline] PHST- 2021/05/09 00:00 [pmc-release] AID - genes12050705 [pii] AID - genes-12-00705 [pii] AID - 10.3390/genes12050705 [doi] PST - epublish SO - Genes (Basel). 2021 May 9;12(5):705. doi: 10.3390/genes12050705.