The Expression And Signaling Of Leptin And Its Receptors In Helicobacter Pylori-associated Gastritis

Background: Helicobacter pylori ( H.pylori ) lives in the extreme environment of the human stomach. It is now firmly established as the principle cause of chronic gastritis and an early risk factor for gastric adenocarcinoma. However, the pathogenic mechanisms are not well defined. Host is gradually proved to be a most important factor in H.pylori-associated diseases. Recently, leptin and its receptors are reported to be present in human stomach. There is a pathophysiologic role for gastric leptin in humans. Gastric leptin may contribute to H.pylori-associated gastritis.Aims: We analyzed the localization and expression of leptin, leptin receptors messenger RNA ( OB-RmRNA ) and the signal transducers and activators of transcription-3 ( STAT-3 ) protein in gastric mucosa of H.pylori-infected and non-infected patients in order to explore the role of gastric leptin in H.pylori-nssociated gastritis and provide a theoretical basis for clinical diagnoses and therapy.Methods: Under endoscope we obtained 45 patients' gastric biopsy specimens, including the corpus and antrum gastric mucosa. We detected the presence of H.pylori by rapid urease tests, Warthin-Starry silver staining and H.pylori-UreA.-PCR. Gastric mucosa leptin content were determined by ELISA. Cellular localization and expression of OB-RmRNA and STAT-3 protein were assessed by in situ hybridization and immunohistochemistry, respectively.Results: We determined 25 cases as H.pylori-positive specimens and 20cases as H.pylori-negative. Leptin content of the corpus gastric mucosa in H.pylori-positive patients was significantly increased (4.62 0.52 ng/ml, n=15) as compared with the H.pylori-negative group (2.50 0.40 ng/ml, n= 9). The presence of OB-RmRNA was shown in parietal cells and antral fundic glandular cells, and its distribution and density were similar in two groups. By immunohistochemistry STAT-3 protein was detectable only in part of parietal cells. The amount of STAT-3 protein immune-staining positive nucleuses was correlated to the gastric leptin level ( r=0.831, P<0.001), and was significant higher in H.pylori-positive group than H.pylori-negative group ( x2=15.72, P<0.001 ). Conclutions: Leptin and its receptors are present in the human gastric mucosa. The coexpression of leptin receptors and STAT-3 are found in parietal cells that, for the first time, argues for STAT-3 as a signal molecule of leptin in human stomach. H.pylori-associated gastritis leads to significant increases in- local leptin concentration in the gastric corpus. These provide further evidence for the involvement of gastric leptin in the contribution to the occurrence and development of H.pyhri-associated gastritis.