Pfkfb1-KO Mouse

Pfkfb1, which encodes the bifunctional enzyme 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase (PFK-2/FBPase-2), plays a crucial role in glucose homeostasis. This enzyme catalyzes the synthesis and degradation of fructose-2,6-bisphosphate, a key metabolite that allosterically regulates the rate-limiting enzyme 6-phosphofructo-1-kinase in the glycolytic pathway, thus controlling the overall rate of glycolysis [2,3,4,7,8].

In multiple myeloma, the STAT3-Pfkfb1 pathway is triggered downstream of LILRB4, which is highly expressed in multiple myeloma cell lines and patient samples. Knockdown of LILRB4 delays the growth of MM cells both in vitro and in vivo, suggesting that the STAT3-Pfkfb1 pathway is important for MM cell proliferation [1]. In sepsis-induced acute lung injury, esculetin inhibits the expression of glycolysis-related genes including Pfkfb1, rebalances M1/M2 macrophage polarization by regulating metabolic reprogramming, and improves the survival rate of rats [5]. In the context of rheumatoid arthritis, synovial fibroblasts under inflammatory conditions can upregulate the mRNA expression level of Pfkfb1 in synovial macrophages, inducing metabolic reprogramming and contributing to chronic inflammation [6].

In conclusion, Pfkfb1 is essential in regulating glycolysis and glucose metabolism. Studies related to Pfkfb1 have shed light on its roles in diseases such as multiple myeloma, sepsis-induced acute lung injury, and rheumatoid arthritis. Understanding the function of Pfkfb1 through these disease-related models can potentially provide new therapeutic strategies for these conditions.

References:

1. Xie, Li, Chen, Chiqi, Zhang, Tinghua, Yu, Zhuo, Zheng, Junke. 2024. LILRB4 regulates multiple myeloma development through STAT3-PFKFB1 pathway. In Cell death & disease, 15, 515. doi:10.1038/s41419-024-06883-4. https://pubmed.ncbi.nlm.nih.gov/39025844/

2. Cosin-Roger, Jesús, Vernia, Santiago, Alvarez, Maria Soledad, Fernández-Alvarez, Ana Julia, Casado, Marta. 2013. Identification of a novel Pfkfb1 mRNA variant in rat fetal liver. In Biochemical and biophysical research communications, 431, 36-40. doi:10.1016/j.bbrc.2012.12.109. https://pubmed.ncbi.nlm.nih.gov/23291237/

3. Bartrons, Ramon, Simon-Molas, Helga, Rodríguez-García, Ana, Manzano, Anna, Martinez-Outschoorn, Ubaldo E. 2018. Fructose 2,6-Bisphosphate in Cancer Cell Metabolism. In Frontiers in oncology, 8, 331. doi:10.3389/fonc.2018.00331. https://pubmed.ncbi.nlm.nih.gov/30234009/

4. Metón, Isidoro, Egea, Miriam, Anemaet, Ida G, Fernández, Felipe, Baanante, Isabel V. 2006. Sterol regulatory element binding protein-1a transactivates 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase gene promoter. In Endocrinology, 147, 3446-56. doi:. https://pubmed.ncbi.nlm.nih.gov/16614080/

5. Chen, Feng, Wang, Ning, Liao, Jiabao, Wen, Weibo, Chen, Fengjuan. . Esculetin rebalances M1/M2 macrophage polarization to treat sepsis-induced acute lung injury through regulating metabolic reprogramming. In Journal of cellular and molecular medicine, 28, e70178. doi:10.1111/jcmm.70178. https://pubmed.ncbi.nlm.nih.gov/39535339/

6. Saeki, Noritaka, Imai, Yuuki. 2020. Reprogramming of synovial macrophage metabolism by synovial fibroblasts under inflammatory conditions. In Cell communication and signaling : CCS, 18, 188. doi:10.1186/s12964-020-00678-8. https://pubmed.ncbi.nlm.nih.gov/33256735/

7. Chesney, Jason. . 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase and tumor cell glycolysis. In Current opinion in clinical nutrition and metabolic care, 9, 535-9. doi:. https://pubmed.ncbi.nlm.nih.gov/16912547/

8. Bartrons, Ramon, Caro, Jaime. . Hypoxia, glucose metabolism and the Warburg's effect. In Journal of bioenergetics and biomembranes, 39, 223-9. doi:. https://pubmed.ncbi.nlm.nih.gov/17661163/