Mouse prepro-epidermal growth factor synthesis by the kidney and other tissues

Abstract

Epidermal growth factor (EGF), a protein comprising 53 amino acids, is derived from a precursor of 1,217 amino acids that includes at least seven EGF-like sequences. EGF has diverse biological activities: it is a potent mitogen for many tissue culture cells, inhibits gastric acid secretion from the intestinal mucosa and promotes healing of the corneal epithelium. EGF given to fetal animals accelerates several developmental processes including palate formation, incisor eruption, eyelid opening and lung maturation. However, the physiological roles of EGF in vivo are unknown. The presence of high-affinity receptors in many fetal and adult tissues suggests that EGF is involved in normal cellular functions. Immunocytochemical studies have revealed the presence of EGF in mouse and human submaxillary glands, rat brain and human intestine. The low levels of EGF in extracts from many tissues may reflect sequestration rather than synthesis of the polypeptide. We show here that several mouse tissues contain preproEGF mRNA and that it is synthesized mainly in the distal tubules of the kidney. PreproEGF does not seem to be processed to EGF or other peptides in this tissue.

Epidermal growth factor (EGF) decreased endothelin‐2 (ET‐2) production in human renal adenocarcinoma cells

“…Although EGF is detectable in many adult mammalian tissues such as mammary and salivary glands, one major site of production is the kidney [26,27]. In humans, intense immunostaining of EGF was observed in the renal medulla [27].…”

“…In humans, intense immunostaining of EGF was observed in the renal medulla [27]. EGF is present abundantly in the kidney as the large precursor protein [26], which is thought to retain EGF-like biological activity [28]. Therefore, it may be possible that EGF or a large precursor form of EGF represses transcription of prepro-ET-2 gone at a physiological condition in the kidney.…”

Epidermal growth factor system is a physiological regulator of development of the mouse fetal submandibular gland and regulates expression of the α6-integrin subunit

“…In the adult mouse SMG, EGF mRNA encodes for a large EGF-precursor protein, proEGF, which is apparently rapidly converted by post-translational processing to EGF of about 6 kDa (Rall et al, 1985). However, in the adult mouse kidney proEGF persists as a large transmembrane protein (Rall et al, 1985;Mroczkowski et al, 1988).…”

Urinary epidermal growth factor concentrations in various human malignancies

“…Urinary EGF originates mostly from the kidneys (Rall et al, 1985;Olsen et al, 1984;Mattila et al, 1986). Thus an increase in urinary EGF concentration could be due to stimulation of renal EGF production by some tumourassociated factor.…”