Saa3, a member of the serum amyloid A (SAA) apolipoprotein family, is involved in multiple biological functions. It functions as a pro-inflammatory cytokine and is associated with pathways such as those related to inflammation, lipid metabolism, and immune cell regulation. Its study is crucial as it impacts various biological processes and disease conditions, and genetic models like KO mouse models are valuable for understanding its functions [1,2,3,4,5,6].

In a DSS-induced IBD mouse model, Saa3-deficient mice showed more severe intestinal fibrosis, suggesting Saa3 deficiency enhances fibroblast activation to myofibroblasts through the HSPB1/NF-κB/TGF-β1/Smads signaling cascade [5]. In the context of sepsis-induced AKI, Saa3 promotes pro-inflammatory macrophage differentiation, and Saa3hi Ccl2hi monocyte-derived infiltrated macrophages are central effector subsets in this process [1]. Ablation of Saa3 in Tsc1Dmp1 mice prevented the reduction of CYP7A1 in the liver and cholesterol elevation in the serum, indicating its role in hepatic cholesterol metabolism [2]. In pancreatic tumors, Saa3-null cancer-associated fibroblasts inhibit tumor growth, while Saa3-competent ones stimulate it, showing Saa3's role in the cross-talk between CAFs and tumor cells [4].

In summary, Saa3 plays essential roles in inflammation, lipid metabolism, and tumor-associated processes. Gene knockout mouse models have been instrumental in revealing its functions in diseases such as sepsis-induced AKI, hypercholesterolaemia, IBD-associated intestinal fibrosis, and pancreatic cancer, providing insights into potential therapeutic strategies for these conditions.