Twist1, a basic helix-loop-helix transcription factor, is crucial in embryonic development and continues to be significant throughout life. It is involved in multiple pathways, most notably the epithelial-mesenchymal transition (EMT) pathway, which is associated with various biological processes and diseases such as organ fibrosis, atherosclerosis, and cancer metastasis [4,5,6]. Genetic models, especially gene knockout (KO) and conditional knockout (CKO) mouse models, have been instrumental in studying its functions.

In fibrotic diseases, specific knockout or pharmacological inhibition of Twist1 in mice significantly ameliorated fibrosis. In the context of intestinal fibrosis in Crohn's disease, Twist1, highly expressed by FAP+ fibroblasts, was found to be a key driver of excessive extracellular matrix (ECM) deposition. Its knockout or inhibition could be a promising strategy for treating CD fibrosis [1]. In kidney fibrosis, fibroblast-specific deletion of Twist1 in mice led to less Prrx1 and TNC protein abundance, interstitial ECM deposition, and kidney inflammation. Inhibition of Twist1 signaling with Harmine also improved ECM deposition in injury models, suggesting Twist1 promotes kidney fibroblast activation and proliferation, contributing to interstitial fibrosis [3]. In atherosclerosis, EC-specific Twist1 knockout mice demonstrated that GATA4-Twist1 signaling promoted EC dysfunction and atherosclerosis development [2].

In conclusion, Twist1 is essential in multiple biological processes, with its dysregulation contributing to various fibrotic diseases and atherosclerosis. Studies using KO/CKO mouse models have revealed its key role in promoting fibrosis in the intestine and kidneys and in the development of atherosclerosis. These findings offer potential therapeutic targets for treating these diseases.