Cfb, short for Complement Factor B, is a key component in the alternative complement pathway. The complement system is crucial for innate immunity, involved in processes like target particle labeling for effective clearance [2]. It plays an essential role in immune responses and is associated with various biological functions related to immunity and disease development. Genetic models, such as gene knockout (KO) mouse models, are valuable for studying Cfb's functions.

In a study on diabetic kidney disease (DKD), Cfb-knockout diabetic mice showed milder tubulointerstitial injury and less ceramide biosynthesis. In vitro, HK-2 cells transfected with CFB siRNA under high-glucose conditions had improved cytokine secretion, reduced endoplasmic reticulum stress, oxidative stress, and cell apoptosis. CFB knockdown downregulated NF-κB p65, which initiates CERS3 transcription, and C3 knockdown abolished CFB-mediated effects on cytokine secretion, NF-κB signaling, and ceramide biosynthesis. This indicates that CFB deficiency inhibits the alternative complement pathway and attenuates kidney damage in DKD by blocking ceramide synthesis via the NF-κB signaling pathway [1].

In conclusion, Cfb is essential in the alternative complement pathway, influencing immune-related functions. The use of Cfb KO mouse models has revealed its role in diseases like DKD, highlighting its potential as a therapeutic target in such conditions.

References:

1. Sun, Zi-Jun, Chang, Dong-Yuan, Chen, Min, Zhao, Ming-Hui. 2022. Deficiency of CFB attenuates renal tubulointerstitial damage by inhibiting ceramide synthesis in diabetic kidney disease. In JCI insight, 7, . doi:10.1172/jci.insight.156748. https://pubmed.ncbi.nlm.nih.gov/36546481/

2. He, Chenglu, Li, Ya, Zhang, Ruixian, Feng, Xingxing, Duan, Yong. 2021. Low CFB expression is independently associated with poor overall and disease-free survival in patients with lung adenocarcinoma. In Oncology letters, 21, 478. doi:10.3892/ol.2021.12739. https://pubmed.ncbi.nlm.nih.gov/33968194/