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Published on: September 23, 2015
Characterization of a putative intrarenal serotonergic system
Jie Xu1, Bing Yao, Xiaofeng Fan
1Division of Nephrology, Vanderbilt Univ. School of Medicine, MCN C3121, 1161 21st St. S., Nashville, TN 37232, USA.
American Journal of Physiology. Renal Physiology
|August 24, 2007
Summary
The kidney synthesizes and utilizes serotonin (5-hydroxytryptamine, 5HT), impacting renal cells. This suggests serotonin may play a role in kidney fibrosis.
Area of Science:
- Nephrology
- Molecular Biology
- Biochemistry
Background:
- Serotonin (5-hydroxytryptamine, 5HT) is a key neurotransmitter with diverse physiological roles.
- Its actions are mediated by various 5-HT receptors and the 5-HT transporter.
- The presence and function of the serotonergic system within the kidney are not fully understood.
Purpose of the Study:
- To investigate the expression and localization of 5-HT receptors and the 5-HT transporter in the kidney.
- To explore the functional consequences of intrarenal 5-HT synthesis and signaling on renal cells.
- To determine the potential role of serotonin in mediating renal fibrosis.
Main Methods:
- Reverse transcription-polymerase chain reaction (RT-PCR) to detect gene expression in renal cell lines.
- Immunohistochemistry to determine protein localization in kidney tissues.
- Cell culture experiments to assess cellular responses to 5-HT stimulation.
- Real-time RT-PCR to quantify gene expression changes.
Main Results:
- The enzymatic pathway for 5-HT synthesis and 5-HT receptors/transporter are present in the renal cortex, particularly in proximal tubules, glomerular epithelial cells, and mesangial cells.
- In cultured proximal tubule cells and podocytes, 5-HT activated ERK1/2 signaling.
- 5-HT increased the expression of connective tissue growth factor (CTGF) and transforming growth factor-beta (TGF-β), key mediators of extracellular matrix accumulation.
- 5-HT also stimulated vascular endothelial growth factor (VEGF) expression in podocytes both in vitro and in vivo.
Conclusions:
- An integrated intrarenal serotonergic system exists, involving 5-HT synthesis, receptors, and transporter.
- Serotonin signaling in renal cells promotes the expression of fibrotic mediators like CTGF and TGF-β.
- These findings suggest a potential role for serotonin as a mediator of renal fibrosis.
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