The synergy of TGF-β and Axl induces CXCL5 secretion causing the infiltration of neutrophils into HCC tissue. Intervention with TGF-β/Axl/CXCL5 signaling may be an effective therapeutic strategy to combat HCC progression in TGF-β-positive patients. This article is protected by copyright. All rights reserved.
Leptin is produced predominantly in adipose tissue but has recently also been found in gastric mucosa. It has been shown that the oral application of leptin induces neuronal activity in the brain stem of rodents. The objective of the present study was to identify this hormone in human saliva and to examine the production and stability of salivary leptin. We have demonstrated production of leptin in salivary glands and oral mucosa by RT-PCR, its storage by immunocytochemistry, and the release of the peptide by RIA . Chromatographic analysis and immunoblotting confirmed the identity of leptin. There is a strong linear correlation (r 2 ؍ 0.78) between leptin concentrations from simultaneously collected saliva and plasma samples (n ؍ 61). Stimulation of saliva flow increases total leptin secretion up to 3-fold (P < 0.001). As to the stability of leptin in gastric fluid, we found the peptide was not degraded above pH 3. S INCE THE DISCOVERY of leptin in 1994, research activities have been directed at understanding the regulation and actions of this peptide hormone. Leptin is the product of the obese gene with a single-chain structure and a molecular mass of 16 kDa. It is produced by differentiated adipocytes (1, 2) as well as in the placenta (3, 4). More recently, storage and secretion of leptin has also been demonstrated in the stomach (5-7). The signal function of leptin on the central nervous system has been the major area of research (8 -12). Leptin influences food intake (e.g. by suppressing neuropeptide Y in the hypothalamus [11], and stimulates energy expenditure and thermogenesis (e.g., by interaction with the adrenal cortex [13,14]). However, specific receptors for leptin have been found ubiquitously in the body (e.g., thyroid gland, adrenal glands, lung, placenta, kidney, liver, and endothelial cells [15][16][17]). This suggests a peripheral role for leptin. Interestingly, a specific leptin receptor was recently identified in the gastric mucosa (6) and in other parts of the gastrointestinal tract (18). To date, the sources of leptin as a gastrointestinal receptor ligand have been only partially investigated.It was therefore an objective of the present study to identify and characterize the presence of leptin in saliva. A second aim was to investigate the regulation of leptin in the salivary glands and its stability under gastric conditions. Materials and Methods Sample materialPlasma and saliva were collected simultaneously from healthy adult males (n ϭ 23; age 28 -80 yr; body mass index [BMI] 20 -50 kg/m 2 ) and females (n ϭ 25; age 22-85 yr; BMI 19.5-54 kg/m 2 ) and healthy adolescents (male: n ϭ 13; female: n ϭ 5; age 10 -18 yr; BMI: 15-39.9 kg/m 2 ) recruited in our hospital, who gave informed consent of participation. None of the volunteers took medication or contraceptives and all participants had fasted for at least 2 h. The study was approved by the Ethics Review Board of the University of Erlangen.Plasma was collected with S-Monovettes, saliva was collected with the Salivette device (both Sarst...
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