S100a8-flox Mouse

S100a8, also known as MRP8, is a Ca2+ binding protein belonging to the S100 family. It often exists as a heterodimer with S100a9 (MRP14). As a Ca2+ sensor constitutively expressed in neutrophils and monocytes, it participates in cytoskeleton rearrangement and arachidonic acid metabolism. During inflammation, the released S100a8/a9 heterodimer plays a critical role in modulating the inflammatory response, for example, by stimulating leukocyte recruitment and cytokine secretion. It also serves as a candidate biomarker for inflammation-associated diseases and has potential as a therapeutic target [1].

In a mouse model of myocardial ischemia-reperfusion (MI/R) injury, knockout of S100a9, a component of the S100a8/a9 heterodimer, markedly decreased cardiomyocyte death and improved heart function, while hematopoietic overexpression of S100a9 exacerbated MI/R injury. Mechanistically, S100a8/a9 caused mitochondrial respiratory dysfunction in cardiomyocytes via Toll-like receptor 4/Erk-mediated Pparg coactivator 1 alpha/nuclear respiratory factor 1 signaling suppression [2]. In diabetic nephropathy, knockdown of S100a8/a9 in tubular epithelial cells of diabetic mice alleviated renal interstitial fibrosis, as high levels of S100a8/a9 activated the TLR4/NF-κB signal pathway, which promoted the epithelial-to-mesenchymal transition (EMT) process and RIF progression [3].

In conclusion, S100a8, mainly in the form of the S100a8/a9 heterodimer, plays a crucial role in inflammation-related biological processes. Gene knockout mouse models, such as S100a9 knockout in MI/R injury and S100a8/a9 knockdown in diabetic nephropathy, have revealed its role in disease-associated mechanisms, highlighting its potential as a therapeutic target for these diseases.