Leptin induces TGF-beta synthesis through functional leptin receptor expressed by human peritoneal mesothelial cell.
Marked increase in leptin concentration in spent peritoneal dialysate has been reported following continuous ambulatory peritoneal dialysis treatment. The present study was designed to determine whether functional leptin receptor is expressed by human peritoneal mesothelial cells and if so, the possible implication in dialysis. Expression of leptin receptors in cultured mesothelial cells and omental tissue was examined. The effect of leptin on the production of transforming growth factor-beta (TGF-beta) by mesothelial cells in the presence or absence of high glucose was determined using in vitro culture model of human peritoneal mesothelial cells and adipocytes. The signaling mechanism involved in leptin-induced TGF-beta synthesis by mesothelial cells was studied. Both mRNA and protein of the full-length leptin receptor are constitutively expressed in mesothelial cells. The leptin receptor expression in mesothelial cells was upregulated by glucose but not leptin. In adipocytes, glucose increased the mRNA expression and synthesis of leptin. The Janus kinase-signal transducers and activation (JAK-STAT) signal transduction pathway in mesothelial cells was activated by either exogenous or adipocytes-derived leptin. Exogenous leptin induced the release of TGF-beta by mesothelial cells. The TGF-beta synthesis induced by leptin was amplified by glucose through increased leptin receptor expression. Our novel findings reveal that functional leptin receptor is present on human peritoneal mesothelial cells. The leptin-induced TGF-beta synthesis in mesothelial cells is associated with the expression of leptin receptor and the activation of the JAK-STAT signal transduction pathway.
Leung
J C K
JC
Department of Medicine, Queen Mary Hospital, The University of Hong Kong, Hong Kong.
Chan
L Y Y
LY
Tang
S C W
SC
Chu
K M
KM
Lai
K N
KN
D002478:Cells, Cultured; D004847:Epithelial Cells / Q000502:physiology*; D006801:Humans; D020738:Leptin / Q000502:physiology*; D010537:Peritoneum / Q000166:cytology*; D011956:Receptors, Cell Surface / Q000096:biosynthesis*; D054411:Receptors, Leptin; D016212:Transforming Growth Factor beta / Q000096:biosynthesis*
C515448:LEPR protein, human; D020738:Leptin; D011956:Receptors, Cell Surface; D054411:Receptors, Leptin; D016212:Transforming Growth Factor beta