Ltbp2-KO Mouse

Ltbp2, known as latent transforming growth factor-β-binding protein 2, is a fibrillin 1 binding component of the microfibril. It is the only LTBP protein that doesn't bind any TGFβ isoforms, yet may interfere with other LTBPs' function or interact with other signaling pathways. Ltbp2 is involved in regulating extracellular matrix (ECM)-related functions and signaling pathways that affect the ECM [4].

Studies on Ltbp2 -/- mice have identified multiple phenotypes. Loss of Ltbp2 impacts bodyweight and fat mass, and affects bone and skin development, with the strength of these tissues being differentially affected. Some tissues like the aorta and lung, despite high Ltbp2 expression, show no developmental or homeostatic phenotype, indicating complex effects of Ltbp2 on development [4].

In human diseases, high Ltbp2 expression in malignant tissues is associated with poor survival in cancer patients, and it's an independent prognostic factor [1]. In gastric cancer, silencing Ltbp2 enhances cisplatin sensitivity, inhibits cell proliferation, and mitigates cisplatin resistance via the NF-κB2/Bcl-3/cyclin D1 pathway [2]. In prostate cancer, Ltbp2 is downregulated and inhibits cancer cell proliferation and metastasis via the PI3K/AKT signaling pathway [3]. In gastric cancer cells, Ltbp2 knockdown promotes ferroptosis through the p62-Keap1-Nrf2 pathway [5]. In a rat model of dilated cardiomyopathy, Ltbp2 silencing attenuates myocardial oxidative stress injury, fibrosis, and remodelling by down-regulating the NF-κB signalling pathway [6]. Also, mutations in the Ltbp2 gene are associated with microspherophakia, a rare inherited eye disorder [7], and plasma Ltbp2 levels may help in the differential diagnosis of connective tissue disease-associated interstitial lung disease and idiopathic pulmonary fibrosis, as well as assess their fibrotic activity [8].

In conclusion, Ltbp2 plays essential roles in development through its effects on ECM-related processes. Its study in KO mouse models and human disease research has revealed its significance in various disease areas, including cancer, heart disease, and eye disorders. Understanding Ltbp2's functions provides insights into disease mechanisms and potential therapeutic targets.