Tinagl1-flox Mouse

Tinagl1, also known as Tubulointerstitial nephritis antigen-like 1, is a matricellular protein. It plays roles in cell adhesion, modulating cell proliferation, migration, and differentiation. It is associated with multiple signaling pathways such as integrin/FAK, EGFR, TGF-β, and ERK [1,2,5,8]. It has significance in various biological processes including wound healing, muscle development, and in disease conditions like cancer, Crohn's Disease, and Helicobacter pylori-associated gastritis [1-9].

In triple-negative breast cancer (TNBC), ectopic expression and therapeutic delivery of Tinagl1 suppress TNBC progression and metastasis by directly binding to integrin α5β1, αvβ1, and EGFR, and inhibiting FAK and EGFR signaling pathways [1]. In Crohn's Disease, mesenteric adipose-derived exosomal TINAGL1 enhances intestinal fibrosis via SMAD4 [2]. In breast cancer, low TINAGL1 expression is a marker for poor prognosis [3]. In diabetes, down-regulated TINAGL1 in fibroblasts impairs wound healing, while exogenous TINAGL1 promotes wound healing in diabetic mice [4]. In hepatocellular carcinoma, TINAGL1 promotes carcinogenesis and metastasis via the TGF-β/Smad3/VEGF axis [5]. In esophageal cancer, YTHDF1 facilitates cancer progression by augmenting m6A-dependent TINAGL1 translation [6]. In Helicobacter pylori infection, TINAGL1 promotes bacterial colonization and gastritis [7]. In muscle development, Tinagl1-deficient mice show reduced body mass, abnormal myofibers, and decreased capillary density, suggesting Tinagl1 is required for normal muscle and capillary development through ERK signaling activation [8]. In tamoxifen-resistant breast cancer cells, Tinagl1 restores tamoxifen sensitivity by blocking EGFR and β1-integrin/FAK signaling pathways [9].

In conclusion, Tinagl1 is a multifunctional protein involved in various biological processes and disease conditions. Studies using gene-knockout or related models have revealed its crucial roles in cancer metastasis, fibrosis, wound healing, muscle development, and bacterial-associated inflammation. Understanding Tinagl1's functions provides potential therapeutic targets for related diseases.