Cebpb-KO Mouse

Cebpb, also known as CCAAT/enhancer binding protein (C/EBP), beta, is a crucial transcription factor involved in multiple biological processes. It participates in various pathways such as JAK1-STAT6, FOXO1/NF-κB, and is associated with adipogenesis, immune cell regulation, and stress-related cancer progression [1,4,5]. Genetic models, especially KO/CKO mouse models, are valuable for studying its functions.

In macrophage autophagy-related studies, macrophage Atg5 cKO mice showed reduced cutaneous inflammation in an AD model. Autophagy deficiency led to CEBPB accumulation, which inhibited JAK1-STAT6 pathway activation and M2 macrophage polarization, alleviating AD [1]. In a study on glioblastoma, the CEBPB+ glioblastoma subcluster specifically drove the formation of M2 tumor-associated macrophages, promoting malignancy growth [2]. For CRC, stress-induced epinephrine promoted CRC development through the CEBPB/TRIM2/P53 axis, and CRC cell-derived CCL20 recruited regulatory T cells to promote chemoresistance via FOXO1/CEBPB/NF-κB signaling [3,4]. Garcinia cambogia attenuated adipogenesis by affecting CEBPB and SQSTM1/p62-mediated selective autophagic degradation of KLF3 [5]. IGF2 deficiency promoted liver aging through mitochondrial dysfunction and upregulated CEBPB signaling [6]. In TNBC, glycolysis restriction repressed a specific CEBPB isoform, affecting myeloid-derived suppressor cells and tumor immunity [7]. MSC-induced lncRNA HCP5 promoted stemness and chemo-resistance of gastric cancer through the miR-3619-5p/AMPK/PGC1α/CEBPB axis [8]. In adenoid cystic carcinoma, the NAT10/CEBPB/vimentin axis promoted malignant phenotypes [9].

In conclusion, Cebpb is essential in processes like immune cell regulation, adipogenesis, and cancer-related pathways. The use of KO/CKO mouse models has revealed its role in diseases such as atopic dermatitis, glioblastoma, CRC, liver aging, TNBC, gastric cancer, and adenoid cystic carcinoma, providing insights into potential therapeutic targets. [1-9]

References:

1. Zhu, Yongcheng, Liu, Yunyao, Ma, Yuxiang, He, Yuan, Qiang, Lei. 2023. Macrophage autophagy deficiency-induced CEBPB accumulation alleviates atopic dermatitis via impairing M2 polarization. In Cell reports, 42, 113430. doi:10.1016/j.celrep.2023.113430. https://pubmed.ncbi.nlm.nih.gov/37963021/

2. Yang, Yongchang, Jin, Xingyu, Xie, Yang, Piao, Yingzhe, Jin, Xun. 2024. The CEBPB+ glioblastoma subcluster specifically drives the formation of M2 tumor-associated macrophages to promote malignancy growth. In Theranostics, 14, 4107-4126. doi:10.7150/thno.93473. https://pubmed.ncbi.nlm.nih.gov/38994023/

3. Zhou, Zili, Shu, Yan, Bao, Haijun, Jian, Chenxing, Shu, Xiaogang. 2022. Stress-induced epinephrine promotes epithelial-to-mesenchymal transition and stemness of CRC through the CEBPB/TRIM2/P53 axis. In Journal of translational medicine, 20, 262. doi:10.1186/s12967-022-03467-8. https://pubmed.ncbi.nlm.nih.gov/35672760/

4. Wang, Dan, Yang, Li, Yu, Weina, Yuan, Weitang, Zhang, Yi. 2019. Colorectal cancer cell-derived CCL20 recruits regulatory T cells to promote chemoresistance via FOXO1/CEBPB/NF-κB signaling. In Journal for immunotherapy of cancer, 7, 215. doi:10.1186/s40425-019-0701-2. https://pubmed.ncbi.nlm.nih.gov/31395078/

5. Han, Joo-Hui, Jang, Keun-Woo, Myung, Chang-Seon. 2021. Garcinia cambogia attenuates adipogenesis by affecting CEBPB and SQSTM1/p62-mediated selective autophagic degradation of KLF3 through RPS6KA1 and STAT3 suppression. In Autophagy, 18, 518-539. doi:10.1080/15548627.2021.1936356. https://pubmed.ncbi.nlm.nih.gov/34101546/

6. Zhou, Xiaohai, Tan, Bowen, Gui, Weiwei, Lin, Xihua, Li, Hong. 2023. IGF2 deficiency promotes liver aging through mitochondrial dysfunction and upregulated CEBPB signaling in D-galactose-induced aging mice. In Molecular medicine (Cambridge, Mass.), 29, 161. doi:10.1186/s10020-023-00752-0. https://pubmed.ncbi.nlm.nih.gov/38017373/

7. Li, Wei, Tanikawa, Takashi, Kryczek, Ilona, Wang, Guobin, Zou, Weiping. 2018. Aerobic Glycolysis Controls Myeloid-Derived Suppressor Cells and Tumor Immunity via a Specific CEBPB Isoform in Triple-Negative Breast Cancer. In Cell metabolism, 28, 87-103.e6. doi:10.1016/j.cmet.2018.04.022. https://pubmed.ncbi.nlm.nih.gov/29805099/

8. Wu, Honglei, Liu, Bin, Chen, Zhaosheng, Li, Guangchun, Zhang, Zhen. 2020. MSC-induced lncRNA HCP5 drove fatty acid oxidation through miR-3619-5p/AMPK/PGC1α/CEBPB axis to promote stemness and chemo-resistance of gastric cancer. In Cell death & disease, 11, 233. doi:10.1038/s41419-020-2426-z. https://pubmed.ncbi.nlm.nih.gov/32300102/

9. Fu, Min, Gao, Qian, Xiao, Mian, Li, Sheng-Lin, Ge, Xi-Yuan. 2024. NAT10/CEBPB/vimentin signalling axis promotes adenoid cystic carcinoma malignant phenotypes in vitro. In Oral diseases, 30, 4341-4355. doi:10.1111/odi.14879. https://pubmed.ncbi.nlm.nih.gov/38287502/