Tinagl1-KO Mouse

Tinagl1, also known as Tubulointerstitial nephritis antigen-like 1, is a matricellular protein. It is involved in multiple biological functions such as cell adhesion, and modulates cell proliferation, migration, and differentiation. It is associated with pathways like integrin/FAK, EGFR, TGF-β, and ERK signaling, which are crucial for normal development and disease-related processes [1,2,5,6].

In breast cancer, Tinagl1 has been well-studied. Ectopic expression and therapeutic delivery of Tinagl1 protein suppress triple-negative breast cancer (TNBC) progression and metastasis by directly binding to integrin α5β1, αvβ1, and EGFR, simultaneously inhibiting FAK and EGFR signaling pathways [1]. Low TINAGL1 mRNA expression is associated with significantly shorter disease-free survival and overall survival in breast cancer patients, and is an independent poor prognostic factor for disease-free survival in invasive breast cancer patients when combined with lymph node positivity [3]. In addition, Tinagl1 can restore tamoxifen sensitivity in tamoxifen-resistant breast cancer cells by blocking the EGFR and β1-integrin/FAK signaling pathways [7].

In Crohn's Disease, mesenteric adipose-derived exosomal TINAGL1 enhances intestinal fibrosis via SMAD4 in the TGF-β signaling pathway [2].

In diabetes, decreased TINAGL1 expression in fibroblasts impairs wound healing, while exogenous TINAGL1 promotes wound healing in diabetic mice [4].

In muscle development, Tinagl1-deficient mice exhibit reduced body mass, calf muscle weights, and a decreasing trend in capillary density in the soleus muscle, indicating that Tinagl1 is required for normal muscle and capillary development through the activation of ERK signaling [6].

In conclusion, Tinagl1 plays essential roles in multiple biological processes and diseases. Studies using gene-knockout or conditional-knockout mouse models, along with other functional studies, have revealed its significance in breast cancer, Crohn's Disease, diabetes-related wound healing, and muscle development. These findings contribute to a better understanding of the molecular mechanisms underlying these diseases and suggest Tinagl1 as a potential therapeutic target [1-4,9,10].