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Several decades ago, researchers Joseph Daniel Jr. from the United States and Henning Beier from Germany independently discovered and reported a new protein called blastokinin, induced by steroid hormones in the uterus of pregnant rabbits. This protein was later named Uteroglobin (UG). UG was found to be widely distributed, not only expressed in the uterus but also detected in the thyroid, respiratory tract, digestive tract, pancreas, prostate, mammary glands, pituitary gland, testes, as well as peripheral blood and urine. In previous studies, UG was also referred to as progesterone-binding protein. The conservation of Recombinant Rat Uteroglobin across species, including mice, rats, hamsters, rabbits, pigs, and humans, suggests its important physiological function. However, its exact physiological function remains unclear. Therefore, extensive in vitro and in vivo experiments have been conducted, including the generation of transgenic mice, to study the structure and function of UG. Surprisingly, although Recombinant Rat Uteroglobin is not expressed in the kidneys, mice with UG gene knockout exhibit significant renal damage, particularly resembling the clinical and pathological features of IgA nephropathy. Thus, Recombinant Rat Uteroglobin has become a new breakthrough in the study of the pathogenesis of kidney diseases.
X-ray diffraction techniques have revealed that Recombinant Rat Uteroglobin is a homodimeric protein consisting of two subunits linked by two disulfide bonds. One disulfide bond is between Cys-3 and Cys-69', and the other is between Cys-3' and Cys-69. The two subunits adopt a reverse equilibrium structure in space. Each subunit consists of 70 amino acids and contains four α-helices with a bend between α-helix 2 and α-helix 3. The dimer forms three cavities in its spatial conformation: C1, C2, and C3. C1 exists between the two subunits and is composed of hydrophobic amino acid residues except for Tyr-21 and Tyr-21'. C2 and C3 are located inside each subunit and are composed of α-helix 1, α-helix 2, and α-helix 3, which contain a large number of hydrophobic amino acids. The structural characteristics of Recombinant Rat Uteroglobin are highly similar among different species.
Initially, it was found that Recombinant Rat Uteroglobin binds to progesterone, polychlorinated biphenyls, and retinol. However, the significance of these bindings remains unclear. Recombinant Rat Uteroglobin may serve as a carrier for certain steroid hormones to reduce their toxic effects on early embryonic development. UG is considered to be a mediator of the immunosuppressive effects associated with progesterone during conception, making it a "natural immunosuppressant." Further research has demonstrated that Recombinant Rat Uteroglobin can protect embryos from maternal immune attacks, suggesting its immunoregulatory role. This immunoregulatory effect can be amplified by transaminases, and it has been found that UG is a substrate for transaminases in related experiments. Recombinant Rat Uteroglobin is primarily expressed in bronchial epithelium, which is exposed to a large number of environmental antigens. This indicates that Recombinant Rat Uteroglobin is a non-specific regulator of immune activity.
[1] Zhang Z, Kundu GC, Yuan CJ, et al. Science, 1997;276:1408-1412
[2] Mukherjee AB, Kundu GC, Mantile-Selvaggi G, et al. Cell Mol Life Sci, 1999;55:771-87
[3] Manjunath R, Chung SI, Mukherjee AB. Biochem Biophys Res Commun, 1984;121:400-407
