Tubulointerstitial Nephritis Antigen-Like 1 Is Expressed in the Uterus and Binds with Integrins in Decidualized Endometrium During Postimplantation in Mice1

Extracellular matrix substrates contribute to both uterine and blastocyst functions during the peri-implantation period. Tubulointerstitial nephritis antigen-like 1 (TINAGL1, also known as adrenocortical zonation factor 1 [AZ-1] or lipocalin 7) is a novel matricellular protein that promotes cell adhesion and spreading. However, the physiological roles of TINAGL1 are still not clearly understood. We examined the expression and localization of TINAGL1 in peri-implantation mouse uteri. During the preimplantation period, TINAGL1 was expressed in the basement membranes of uterine luminal epithelial cells on Days 1 and 2 of pregnancy, while its expression levels declined after Day 3. In the whole uteri, the expression levels of Tinagl1 mRNA and TINAGL1 protein were similar on Days 1-4 of pregnancy. In contrast, the expression of Tinagl1 mRNA and TINAGL1 protein increased in postimplantation uteri. From Days 6 to 8, TINAGL1 was markedly expressed in the decidual endometrium. TINAGL1 is a ligand for integrins and promotes cell adhesion in cultured cells. Therefore, to address whether TINAGL1 interacts with integrins in the uterus, immunohistochemical analysis and immunoprecipitation were performed. Immunohistochemical analysis showed that ITGA2, ITGA5, and ITGB1 were expressed in stromal cells around the implanted embryos on Days 7 and 8. Biacore and immunoprecipitation analysis determined that TINAGL1 linked with ITGA5 and ITGB1 in the decidual endometrium. These results suggest that Tinagl1 functions during the postimplantation period; in particular, it associates with ITGA5B1 in the decidualized uterine endometrium.