PMID- 36835615 OWN - NLM STAT- MEDLINE DCOM- 20230228 LR - 20230301 IS - 1422-0067 (Electronic) IS - 1422-0067 (Linking) VI - 24 IP - 4 DP - 2023 Feb 20 TI - GPR41 Regulates the Proliferation of BRECs via the PIK3-AKT-mTOR Pathway. LID - 10.3390/ijms24044203 [doi] LID - 4203 AB - Short-chain fatty acids (SCFAs) play a pivotal role in regulating the proliferation and development of bovine rumen epithelial cells (BRECs). G protein-coupled receptor 41 (GPR41) is involved in the signal transduction in BRECs as a receptor for SCFAs. Nevertheless, the impact of GPR41 on the proliferation of BRECs has not been reported. The results of this research showed that the knockdown of GPR41 (GRP41KD) decreased BRECs proliferation compared with the wild-type BRECs (WT) (p < 0.001). The RNA sequencing (RNA-seq) analysis showed that the gene expression profiles differed between WT and GPR41KD BRECs, with the major differential genes enriched in phosphatidylinositol 3-kinase (PIK3) signaling, cell cycle, and amino acid transport pathways (p < 0.05). The transcriptome data were further validated by Western blot and qRT-PCR. It was evident that the GPR41KD BRECs downregulated the level of the PIK3-Protein kinase B (AKT)-mammalian target of the rapamycin (mTOR) signaling pathway core genes, such as PIK3, AKT, eukaryotic translation initiation factor 4E binding protein 1 (4EBP1) and mTOR contrasted with the WT cells (p < 0.01). Furthermore, the GPR41KD BRECs downregulated the level of Cyclin D2 p < 0.001) and Cyclin E2 (p < 0.05) compared with the WT cells. Therefore, it was proposed that GPR41 may affect the proliferation of BRECs by mediating the PIK3-AKT-mTOR signaling pathway. FAU - Meng, Zitong AU - Meng Z AUID- ORCID: 0000-0001-6913-1162 AD - Institute of Animal Culture Collection and Application, College of Animal Science and Technology, Yangzhou University, Yangzhou 225009, China. FAU - Tan, Dejin AU - Tan D AD - Institute of Animal Culture Collection and Application, College of Animal Science and Technology, Yangzhou University, Yangzhou 225009, China. FAU - Cheng, Zhiqiang AU - Cheng Z AUID- ORCID: 0000-0003-4911-6285 AD - Institute of Animal Culture Collection and Application, College of Animal Science and Technology, Yangzhou University, Yangzhou 225009, China. FAU - Jiang, Maocheng AU - Jiang M AUID- ORCID: 0000-0002-4533-101X AD - Institute of Animal Culture Collection and Application, College of Animal Science and Technology, Yangzhou University, Yangzhou 225009, China. FAU - Zhan, Kang AU - Zhan K AD - Institute of Animal Culture Collection and Application, College of Animal Science and Technology, Yangzhou University, Yangzhou 225009, China. AD - Institutes of Agricultural Science and Technology Development, Yangzhou University, Yangzhou 225009, China. AD - Joint International Research Laboratory of Agriculture and Agri-Product Safety, The Ministry of Education of China, Yangzhou University, Yangzhou 225009, China. LA - eng PT - Journal Article DEP - 20230220 PL - Switzerland TA - Int J Mol Sci JT - International journal of molecular sciences JID - 101092791 RN - 0 (Fatty Acids, Volatile) RN - EC 2.7.1.137 (Phosphatidylinositol 3-Kinase) RN - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt) RN - EC 2.7.11.1 (TOR Serine-Threonine Kinases) SB - IM MH - Animals MH - Cattle MH - Cell Proliferation MH - Epithelial Cells/metabolism MH - Fatty Acids, Volatile/metabolism MH - *Phosphatidylinositol 3-Kinase/metabolism MH - *Proto-Oncogene Proteins c-akt/metabolism MH - Rumen MH - TOR Serine-Threonine Kinases/metabolism PMC - PMC9963637 OTO - NOTNLM OT - BRECs OT - GPR41 OT - PIK3-AKT-mTOR OT - proliferation COIS- The authors declare no conflict of interest. EDAT- 2023/02/26 06:00 MHDA- 2023/03/03 06:00 PMCR- 2023/02/20 CRDT- 2023/02/25 02:56 PHST- 2022/12/02 00:00 [received] PHST- 2023/02/06 00:00 [revised] PHST- 2023/02/16 00:00 [accepted] PHST- 2023/02/25 02:56 [entrez] PHST- 2023/02/26 06:00 [pubmed] PHST- 2023/03/03 06:00 [medline] PHST- 2023/02/20 00:00 [pmc-release] AID - ijms24044203 [pii] AID - ijms-24-04203 [pii] AID - 10.3390/ijms24044203 [doi] PST - epublish SO - Int J Mol Sci. 2023 Feb 20;24(4):4203. doi: 10.3390/ijms24044203.