Thbs1, or thrombospondin-1, is a secreted matricellular protein encoded by the THBS1 gene. It functions as a stress-and injury-induced mediator, influencing cellular attachment dynamics and extracellular matrix protein production. Thbs1 is involved in multiple pathways, such as activating the endoplasmic reticulum stress effector PERK and regulating the TGFβ-Smad2/3-ATF4 signaling pathway. It plays a significant role in various biological processes and disease conditions, making genetic models like knockout (KO) mice crucial for its study [1,3].

In KO mouse models, Thbs1 -/- mice show greater cardiac hypertrophy with pressure overload stimulation and reduced fasting-induced atrophy, indicating that Thbs1 may contribute to cardiac atrophy [1]. Similarly, Thbs1 -/- mice have significantly reduced levels of denervation-and caloric restriction-mediated muscle atrophy, suggesting its role in skeletal muscle mass regulation through the TGFβ-Smad3-ATF4 signaling pathway [3]. In the context of cancer, THBS1-producing monocyte-like cells contribute to immunosuppression and metastasis in colorectal cancer, and targeting THBS1 in the tumor microenvironment renders tumors partially sensitive to immune checkpoint inhibitors and anti-cancer drugs [2].

In conclusion, Thbs1 plays essential roles in regulating cardiomyocyte size, skeletal muscle mass, and cancer-related immunosuppression and metastasis. The use of Thbs1 KO mouse models has provided valuable insights into its functions in heart diseases, muscle atrophy, and colorectal cancer, highlighting its potential as a therapeutic target in these disease areas.