Gzma-KO Mouse

GZMA, also known as granzyme A, is a serine protease. It is involved in cytotoxic lymphocyte-mediated immunity and is thought to play a role in various cell death-related processes and immune-related pathways [2]. It has significance in maintaining normal physiological functions and is closely associated with multiple disease-related biological processes.

In inflammatory bowel disease (IBD), GZMA was found to suppress GPX4-mediated ferroptosis, promoting intestinal epithelial barrier function by enhancing CDX2-mediated cell differentiation, which induced the expression of Occludin and Zonula Occludens-1. Administration of GZMA could alleviate DSS-induced colitis in vivo [1].

In chronic apical periodontitis, inhibition of GZMA using crRNA/Cas13d led to decreased osteoclast cell proliferation, increased apoptosis, and changes in miR-25-3p, TGF-β, and PAR1 expression within the PARs pathway, suggesting GZMA as a potential therapeutic target [3].

In hepatocellular carcinoma, GZMA secreted by cytotoxic cells interacted with F2R expressed by tumor cells, activating the JAK2/STAT1 signaling pathway to induce tumor suppression, and low GZMA and F2R expression in tumor tissues was associated with poor prognosis [4].

In summary, GZMA has diverse functions in different biological processes and disease conditions. Its role in promoting intestinal epithelial barrier function in IBD, regulating osteoclast function in chronic apical periodontitis, and affecting tumor suppression in hepatocellular carcinoma, among others, highlights its importance. The use of genetic models such as those in the above-mentioned studies helps to uncover these functions, providing potential therapeutic directions for related diseases.