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Am J Physiol Renal Physiol (August 22, 2007). doi:10.1152/ajprenal.00246.2007
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Submitted on May 29, 2007
Accepted on August 21, 2007

Characterization of a Putative Intrarenal Serotonergic System

Jie Xu1, Yao Bing2, Xaiofeng Fan1, Melissa Langworthy3, Ming-Zhi Zhang1, and Raymond Harris4*

1 Medicine, Vanderbilt University, Nashville, Tennessee, United States
2 Medicine, Division of Nephrology, Vanderbilt University, Nashville, Tennessee, United States
3 Cell and Devekiomental Biology, Vanderbilt University, Nashville, Tennessee, United States; Medicine, Vanderbilt University, Nashville, Tennessee, United States
4 Vanderbilt University School of Medicine, United States

* To whom correspondence should be addressed. E-mail: ray.harris{at}vanderbilt.edu.

Serotonin (5-hydroxytryptamine, 5HT) acts through multiple G-protein-coupled serotonin receptors, and its activity is also regulated by the serotonin transporter. The current studies report the expression and localization of the serotonin receptors and transporter in the kidney. In addition, the enzymatic pathway mediating serotonin synthesis is present in renal cortex, especially in the proximal tubules and glomerular epithelial cells and mesangial cells. Expression of the serotonin receptors and serotonin transporter was detected by RT-PCR in cell lines of these cell types. In cultured proximal tubule cells and podocytes, serotonin activated ERK1/2 and increased the expression of Connective Tissue Growth Factor (CTGF) and Transforming Growth Factor {beta} (TGF-{beta}), two key mediators of extracellular matrix accumulation. Immunohistochemistry and real time RT-PCR studies also indicated that serotonin stimulated expression of Vascular Endothelial Growth Factor (VEGF) 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 serotonin as a mediator of renal fibrosis in the kidney.




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