Nr0b2, also known as Small Heterodimer Partner (SHP), is an orphan nuclear receptor that acts as a transcriptional regulator. It controls various metabolic processes such as cholesterol homeostasis and lipid metabolism, and is involved in pathways like the FGF15/FGF19-NR0B2/SHP-TFEB pathway regulating postprandial lipids by lipophagic activation [5]. It has significance in multiple biological processes and is a potential therapeutic target for several diseases [1,3].

In gastric diseases, its expression levels are altered, with reduction in gastric cancer and increase in gastritis. A causal relationship between Nr0B2 expression and the risk of gastric diseases has been confirmed, and low expression is a risk factor for poor prognosis in gastric cancer [1]. In breast cancer, Nr0B2 in myeloid immune cells impairs the expansion of regulatory T cells (Tregs), and mice lacking Nr0B2 exhibit accelerated tumor growth, indicating its role in tumor growth regulation [4]. In primary sclerosing cholangitis, Nr0B2 is upregulated in cholangiocytes, highlighting a metabolic and premalignant reprogramming of this cell type [2].

In conclusion, Nr0B2 is a crucial transcriptional regulator involved in various metabolic processes. Studies, including those using gene-knockout mouse models, have revealed its significance in diseases such as gastric diseases, breast cancer, and primary sclerosing cholangitis. These findings provide insights into potential therapeutic strategies targeting Nr0B2 for treating related diseases.

References:

1. Li, Zhengwen, Xu, Lijia, Huang, Dongliang, Haenen, Guido R M M, Zhang, Ming. 2024. NR0B2 Is a Key Factor for Gastric Diseases: A GEO Database Analysis Combined with Drug-Target Mendelian Randomization. In Genes, 15, . doi:10.3390/genes15091210. https://pubmed.ncbi.nlm.nih.gov/39336801/

2. Desterke, Christophe, Chung, Chuhan, Pan, David, Azoulay, Daniel, Feray, Cyrille. 2022. Early Deregulation of Cholangiocyte NR0B2 During Primary Sclerosing Cholangitis. In Gastro hep advances, 2, 49-62. doi:10.1016/j.gastha.2022.07.023. https://pubmed.ncbi.nlm.nih.gov/39130146/

3. Vidana Gamage, Hashni Epa, Albright, Samuel T, Smith, Amanda J, Hergenrother, Paul J, Nelson, Erik R. 2024. Development of NR0B2 as a therapeutic target for the re-education of tumor associated myeloid cells. In Cancer letters, 597, 217086. doi:10.1016/j.canlet.2024.217086. https://pubmed.ncbi.nlm.nih.gov/38944231/

4. Vidana Gamage, Hashni Epa, Shahoei, Sayyed Hamed, Wang, Yu, Apetoh, Lionel, Nelson, Erik R. 2024. NR0B2 re-educates myeloid immune cells to reduce regulatory T cell expansion and progression of breast and other solid tumors. In Cancer letters, 597, 217042. doi:10.1016/j.canlet.2024.217042. https://pubmed.ncbi.nlm.nih.gov/38908543/

5. Seok, Sunmi, Kemper, Jongsook Kim. 2022. Paradoxical feeding activation of gut lipophagy by FGF15/FGF19-NR0B2/SHP-TFEB. In Autophagy, 19, 742-743. doi:10.1080/15548627.2022.2108296. https://pubmed.ncbi.nlm.nih.gov/35913833/