PMID- 34948427 OWN - NLM STAT- MEDLINE DCOM- 20220131 LR - 20220131 IS - 1422-0067 (Electronic) IS - 1422-0067 (Linking) VI - 22 IP - 24 DP - 2021 Dec 20 TI - KRAS Affects Adipogenic Differentiation by Regulating Autophagy and MAPK Activation in 3T3-L1 and C2C12 Cells. LID - 10.3390/ijms222413630 [doi] LID - 13630 AB - Kirsten rat sarcoma 2 viral oncogene homolog (Kras) is a proto-oncogene that encodes the small GTPase transductor protein KRAS, which has previously been found to promote cytokine secretion, cell survival, and chemotaxis. However, its effects on preadipocyte differentiation and lipid accumulation are unclear. In this study, the effects of KRAS inhibition on proliferation, autophagy, and adipogenic differentiation as well as its potential mechanisms were analyzed in the 3T3-L1 and C2C12 cell lines. The results showed that KRAS was localized mainly in the nuclei of 3T3-L1 and C2C12 cells. Inhibition of KRAS altered mammalian target of rapamycin (Mtor), proliferating cell nuclear antigen (Pcna), Myc, peroxisome proliferator-activated receptor gamma (PPARgamma), CCAAT/enhancer binding protein beta (C/ebp-beta), diacylglycerol O-acyltransferase 1 (Dgat1), and stearoyl-coenzyme A desaturase 1 (Scd1) expression, thereby reducing cell proliferation capacity while inducing autophagy, enhancing differentiation of 3T3-L1 and C2C12 cells into mature adipocytes, and increasing adipogenesis and the capacity to store lipids. Moreover, during differentiation, KRAS inhibition reduced the levels of extracellular regulated protein kinases (ERK), c-Jun N-terminal kinase (JNK), p38, and phosphatidylinositol 3 kinase (PI3K) activation. These results show that KRAS has unique regulatory effects on cell proliferation, autophagy, adipogenic differentiation, and lipid accumulation. FAU - Yu, Wenjie AU - Yu W AD - Department of Laboratory Animals, Jilin Provincial Key Laboratory of Animal Model, Jilin University, Changchun 130062, China. FAU - Chen, Cheng-Zhen AU - Chen CZ AD - Department of Laboratory Animals, Jilin Provincial Key Laboratory of Animal Model, Jilin University, Changchun 130062, China. FAU - Peng, Yanxia AU - Peng Y AD - Department of Laboratory Animals, Jilin Provincial Key Laboratory of Animal Model, Jilin University, Changchun 130062, China. FAU - Li, Ze AU - Li Z AD - Department of Laboratory Animals, Jilin Provincial Key Laboratory of Animal Model, Jilin University, Changchun 130062, China. FAU - Gao, Yan AU - Gao Y AD - Department of Laboratory Animals, Jilin Provincial Key Laboratory of Animal Model, Jilin University, Changchun 130062, China. FAU - Liang, Shuang AU - Liang S AD - Department of Laboratory Animals, Jilin Provincial Key Laboratory of Animal Model, Jilin University, Changchun 130062, China. FAU - Yuan, Bao AU - Yuan B AUID- ORCID: 0000-0003-3490-0755 AD - Department of Laboratory Animals, Jilin Provincial Key Laboratory of Animal Model, Jilin University, Changchun 130062, China. FAU - Kim, Nam-Hyung AU - Kim NH AD - Department of Laboratory Animals, Jilin Provincial Key Laboratory of Animal Model, Jilin University, Changchun 130062, China. AD - Department of Animal Science, Chungbuk National University, Cheongju 361-763, Chungbuk, Korea. FAU - Jiang, Hao AU - Jiang H AUID- ORCID: 0000-0003-2008-6166 AD - Department of Laboratory Animals, Jilin Provincial Key Laboratory of Animal Model, Jilin University, Changchun 130062, China. FAU - Zhang, Jia-Bao AU - Zhang JB AUID- ORCID: 0000-0001-8533-4744 AD - Department of Laboratory Animals, Jilin Provincial Key Laboratory of Animal Model, Jilin University, Changchun 130062, China. LA - eng GR - CARS-37/China Agriculture Research System of MOF and MARA/ PT - Journal Article DEP - 20211220 PL - Switzerland TA - Int J Mol Sci JT - International journal of molecular sciences JID - 101092791 RN - 0 (CCAAT-Enhancer-Binding Protein-beta) RN - 0 (Cebpb protein, mouse) RN - 0 (PPAR gamma) RN - 0 (Proliferating Cell Nuclear Antigen) RN - EC 1.14.19.1 (Scd1 protein, mouse) RN - EC 1.14.19.1 (Stearoyl-CoA Desaturase) RN - EC 2.3.1.20 (Dgat1 protein, mouse) RN - EC 2.3.1.20 (Diacylglycerol O-Acyltransferase) RN - EC 2.7.11.1 (TOR Serine-Threonine Kinases) RN - EC 2.7.11.24 (Extracellular Signal-Regulated MAP Kinases) RN - EC 2.7.11.24 (JNK Mitogen-Activated Protein Kinases) RN - EC 3.6.5.2 (Hras protein, mouse) RN - EC 3.6.5.2 (Proto-Oncogene Proteins p21(ras)) SB - IM MH - 3T3 Cells MH - *Adipogenesis MH - Animals MH - *Autophagy MH - CCAAT-Enhancer-Binding Protein-beta/genetics MH - *Cell Proliferation MH - Cells, Cultured MH - Diacylglycerol O-Acyltransferase/genetics MH - Extracellular Signal-Regulated MAP Kinases/genetics/metabolism MH - Fibroblasts/*metabolism/physiology MH - Gene Expression Regulation MH - JNK Mitogen-Activated Protein Kinases/genetics/metabolism MH - Lipid Metabolism MH - Mice MH - Myoblasts/*metabolism/physiology MH - PPAR gamma/genetics MH - Proliferating Cell Nuclear Antigen/genetics MH - Proto-Oncogene Proteins p21(ras)/metabolism/*physiology MH - *Signal Transduction MH - Stearoyl-CoA Desaturase/genetics MH - TOR Serine-Threonine Kinases/genetics PMC - PMC8707842 OTO - NOTNLM OT - KRAS OT - MAPK OT - PI3K OT - adipogenic differentiation OT - autophagy OT - lipid accumulation COIS- The authors declare no conflict of interest. EDAT- 2021/12/25 06:00 MHDA- 2022/02/01 06:00 PMCR- 2021/12/20 CRDT- 2021/12/24 01:17 PHST- 2021/09/07 00:00 [received] PHST- 2021/12/15 00:00 [revised] PHST- 2021/12/17 00:00 [accepted] PHST- 2021/12/24 01:17 [entrez] PHST- 2021/12/25 06:00 [pubmed] PHST- 2022/02/01 06:00 [medline] PHST- 2021/12/20 00:00 [pmc-release] AID - ijms222413630 [pii] AID - ijms-22-13630 [pii] AID - 10.3390/ijms222413630 [doi] PST - epublish SO - Int J Mol Sci. 2021 Dec 20;22(24):13630. doi: 10.3390/ijms222413630.