Characterization of a putative intrarenal serotonergic system.
Serotonin [5-hydroxytryptamine (5HT)] acts through multiple G protein-coupled 5-HT receptors, and its activity is also regulated by the 5-HT transporter. The current studies report the expression and localization of the 5-HT receptors and transporter in the kidney. In addition, the enzymatic pathway mediating 5-HT synthesis is present in renal cortex, especially in the proximal tubules and glomerular epithelial cells and mesangial cells. Expression of the 5-HT receptors and 5-HT transporter was detected by RT-PCR in cell lines of these cell types. In cultured proximal tubule cells and podocytes, 5-HT activated ERK1/2 and increased the expression of connective tissue growth factor and transforming growth factor-beta, two key mediators of extracellular matrix accumulation. Immunohistochemistry and real-time RT-PCR studies also indicated that 5-HT stimulated expression of vascular endothelial growth factor in podocytes in vitro and in vivo. Therefore, these results indicate the presence of an integrated intrarenal serotonergic system and suggest a possible role for 5-HT as a mediator of renal fibrosis in the kidney.
Xu
Jie
J
Division of Nephrology, Vanderbilt Univ. School of Medicine, MCN C3121, 1161 21st St. S., Nashville, TN 37232, USA.
Yao
Bing
B
Fan
Xiaofeng
X
Langworthy
Melissa M
MM
Zhang
Ming-Zhi
MZ
Harris
Raymond C
RC
D000818:Animals; D001142:Aromatic-L-Amino-Acid Decarboxylases / Q000378:metabolism*; D002460:Cell Line; D055513:Connective Tissue Growth Factor; D017874:Immediate-Early Proteins / Q000378:metabolism; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism; D007672:Kidney Cortex / Q000378:metabolism*; D007687:Kidney Tubules, Proximal / Q000166:cytology / Q000378:metabolism; D008297:Male; D051379:Mice; D020929:Mitogen-Activated Protein Kinase Kinases / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D050199:Podocytes / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D044402:Receptor, Serotonin, 5-HT2A / Q000378:metabolism; D011985:Receptors, Serotonin / Q000378:metabolism*; D012701:Serotonin / Q000378:metabolism / Q000494:pharmacology; D050486:Serotonin Plasma Membrane Transport Proteins / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology; D014018:Tissue Distribution; D016212:Transforming Growth Factor beta / Q000378:metabolism; D014365:Tryptophan Hydroxylase / Q000378:metabolism*; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
C526318:CCN2 protein, mouse; C526316:CCN2 protein, rat; D017874:Immediate-Early Proteins; D036341:Intercellular Signaling Peptides and Proteins; D044402:Receptor, Serotonin, 5-HT2A; D011985:Receptors, Serotonin; D050486:Serotonin Plasma Membrane Transport Proteins; D016212:Transforming Growth Factor beta; D042461:Vascular Endothelial Growth Factor A; D055513:Connective Tissue Growth Factor; D012701:Serotonin; D014365:Tryptophan Hydroxylase; D020929:Mitogen-Activated Protein Kinase Kinases; D001142:Aromatic-L-Amino-Acid Decarboxylases