Rat fetuin: distribution of protein and mRNA in embryonic and neonatal rat tissues

Abstract

Fetuin is a serum protein widely distributed in the animal kingdom and found in all mammalian species so far investigated. It is mainly a fetal protein, in the sense that the highest concentrations are found in serum and body fluids of embryos and fetuses. In order to elucidate possible biological functions of fetuin, we have studied its synthesis and distribution during the prenatal development of the rat with immunohistochemistry and in situ hybridization. We have isolated fetuin from rat serum and produced an antibody against this protein. In situ hybridization was performed using a 375-nucleotides-long digoxigenin-labeled riboprobe. Fetuin was unevenly distributed in all organ systems during development, with the most pronounced expression at E 10Fetuin is a serum protein widely distributed in the animal kingdom and found in all mammalian species so far investigated. It is mainly a fetal protein, in the sense that the highest concentrations are found in serum and body fluids of embryos and fetuses. In order to elucidate possible biological functions of fetuin, we have studied its synthesis and distribution during the prenatal development of the rat with immunohistochemistry and in situ hybridization. We have isolated fetuin from rat serum and produced an antibody against this protein. In situ hybridization was performed using a 375-nucleotides-long digoxigenin-labeled riboprobe. Fetuin was unevenly distributed in all organ systems during development, with the most pronounced expression at E16-E18. Fetuin expression was present in germinal cell populations, e.g., in the basal layer in the skin, in the germinal cell populations in the brain anlage and the gonads, and it was heavily expressed in the fetal hemopoietic liver. Furthermore, fetuin was expressed in the gastrointestinal epithelium prior to the development of glands and crypts. Fetuin was widely distributed in mesenchymal derived tissues, e.g., bone and muscle. In the developing kidney fetuin was heavily expressed is both mesenchymal condensations and glomerular anlages. Thus, fetuin was located in cells or structures undergoing differentiation and transformation. As fetuin has been shown previously to interfere with hormone signaling of transforming growth factor-beta, insulin and hepatocyte-growth factor, fetuin might be involved in cell differentiation and tissue transformation during the initial histogenesis, i.e., the time period in which cellular phenotypic characteristics are established.

Molecular Characterization and Expression Pattern of Fetuin-B in Gibel Carp (Carassius auratus gibelio)

“…A similar extra-hepatic expression pattern during the embryonic stage was also reported in mammalian fetuin-A (Terkelsen et al 1998;Dziegielewska et al 2000). The overlapping roles of fetuin-B and fetuin-A were also revealed in mammals (Olivier et al 2000;Denecke et al 2003).…”

“…In mouse embryo, fetuin-A transcript could also be detected in a number of developing tissues and organs other than hepatic tissue, such as heart, lung, kidney, nervous system, and limb buds during the particular stages (Yang et al 1992). In fetal neonatal rats and fetal sheep, the presence of fetuin-A mRNA was also found in many of the germinal cell populations of developing tissues and organs including brain, kidney, haemopoietic liver, early gastrointestinal epithelium, bone, and muscle (Saunders et al 1994;Terkelsen et al 1998), and its protein was predominantly in the developing central and peripheral nervous system, cerebrospinal fluid, and plasma (Kitchener et al 1999;Dziegielewska et al 2000). It has been demonstrated that fetuin-A plays important roles during developmental processes, including osteogenesis, myotubule (Yang et al 1992), fetal brain, and nervous system development (Kitchener et al 1999;Dziegielewska et al 2000).…”

Discovery of a High Molecular Weight Complex of Calcium, Phosphate, Fetuin, and Matrix γ-Carboxyglutamic Acid Protein in the Serum of Etidronate-treated Rats

“…This possibility is supported by the observation that fetuin is synthesized by osteoblasts in fetal rat bone (28,29) and by fetal rat osteoblasts in cell culture (28). A number of studies have, however, failed to find evidence for the synthesis of fetuin or for the expression of mRNA for fetuin in the bones of adult rats (19, 29 -31).…”

Role of Fetuin-A in Injury and Infection

“…During fetal development, it is expressed in most organs including the liver, kidney, gastrointestinal tract, skin and brain (Terkelsen et al 1998;Kitchener et al 1997;Dziegielewska et al 2000;Kitchener et al 1999). In adults however, fetuin-A is produced primarily by the liver, and its synthesis is divergently regulated during injury or infection, classifying it as a negative or positive APP.…”