Expression of a novel member of the TGF-β superfamily, growth/differentiation factor-15/macrophage-inhibiting cytokine-1 (GDF-15/MIC-1) in adult rat tissues

Abstract

We have cloned a novel member of the transforming growth factor-beta (TGF-beta) superfamily from a human placental cDNA library. The sequence is identical to five very recently published sequences, of which only one (macrophage inhibitory cytokine-1, MIC-1) has been characterized in terms of function. In light of the present data demonstrating the wide distribution of the mRNA and putative multifunctionality, we propose to name this molecule growth/differentiation factor-15/MIC-1 (GDF-15/MIC-1). The deduced amino acid sequence reveals typical features of a secreted molecule. The epithelium of the choroid plexus is the only site in the adult brain expressing detectable levels of GDF-15/MIC-1 mRNA. Many epithelia of non-neural tissues including those of the prostate and intestinal mucosa, bronchi and bronchioli, secretory tubuli of the submandibular gland, and lactating mammary gland are prominent sites of GDF-15/MIC-1 synthesis. GDF-15/MIC-1 is also strongly expressed by macrophages in the adrenal gland. Thus, GDF-15/MIC-1, like many other members of the TGF-beta superfamily, is widely distributed in adult tissues, being most strongly expressed in epithelial cells and macrophages.

GDF15 is elevated in mice following retinal ganglion cell death and in glaucoma patients

“…We also examined Tgfb2 gene expression in the retina because of its previously described association with human primary open angle glaucoma (POAG) (11)(12)(13) and because GDF15 is a member of the TGF-β superfamily (14). In terms of rodent models of glaucoma, no rodent glaucoma model has convincingly demonstrated elevated Tgfb2 gene expression in the retina.…”

Bone marrow mesenchymal stem cells are abnormal in multiple myeloma

“…GDF15 is a divergent member of the TGFb superfamily. 48 In normal human subjects, it is highly expressed in the placenta and its serum concentration increases during pregnancy. 49 GDF15 concentration is increased in the serum of patients with prostate, colorectal or pancreatic cancers 50,51 and was recently described as one of the 20 best biomarkers of numerous tumors.…”

The murine growth differentiation factor 15 is not essential for systemic iron homeostasis in phlebotomized mice

“…[4][5][6][7] GDF15 is expressed in several organs, including liver, lung, kidney, and exocrine glands. 8,9 In mice, GDF15 acts as a cardioprotective factor released by the myocardium, and as a neurotrophic factor for midbrain dopaminergic neurons. [10][11][12] Mice treated with systemic GDF15 and transgenic mice overexpressing GDF15 show hypophagia and reduced body weight.…”