Role of serotonin in the regulation of renal proximal tubular epithelial cells.
In various renal injuries, tissue damage occurs and platelet activation is observed. Recent studies suggest that some factors, such as serotonin, are released into microenvironment upon platelet activation following renal injury. In the present study, we aimed to investigate whether platelets and platelet-released serotonin are involved in the functional regulation of renal proximal tubular epithelial cells (PTECs). PTECs were obtained by primary cell culture and treated with platelet lysate (PL) (2 × 10(6)/mL, 4 × 10(6)/mL, 8 × 10(6)/mL) or serotonin (1 μM or 5 μM) for 12 or 24 h. Phenotypic transdifferentiation of epithelial cells into myofibroblasts were demonstrated under light microscope and confirmed by the determination of α-smooth muscle actin gene expression. Serotonin and PL were shown to induce epithelial-mesenchymal transdifferentiation of PTECs. After stimulation of PTECs with serotonin or PL, matrix metalloproteinase-2, tissue inhibitor of metalloproteinase-1, and collagen-α1 gene expressions, which were reported to be elevated in renal injury, were determined by real-time PCR and found to be upregulated. Expressions of some inflammatory cytokines such as tumor necrosis factor-α, interleukin-6, and transforming growth factor-β1 were found to be increased in both protein and gene levels. Recently there is no published report on the effect of serotonin on renal PTECs. Results obtained in this study have lightened the role of serotonin and platelet-mediated effects of serotonin on fibrotic and inflammatory processes in PTECs.
a Department of Biochemistry, Faculty of Pharmacy , Hacettepe University , Ankara , Turkey.
Acelya
A
Erikci
a Department of Biochemistry, Faculty of Pharmacy , Hacettepe University , Ankara , Turkey.
Gulberk
G
Ucar
a Department of Biochemistry, Faculty of Pharmacy , Hacettepe University , Ankara , Turkey.
Samiye
S
Yabanoglu-Ciftci
D000818:Animals; D001792:Blood Platelets / Q000378:metabolism*; D024042:Collagen Type I / Q000378:metabolism; D000090602:Collagen Type I, alpha 1 Chain; D004847:Epithelial Cells / Q000502:physiology*; D058750:Epithelial-Mesenchymal Transition; D005355:Fibrosis / Q000378:metabolism; D007249:Inflammation / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D007687:Kidney Tubules, Proximal / Q000166:cytology*; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D051379:Mice; D058628:Myofibroblasts / Q000502:physiology*; D061251:Primary Cell Culture; D012701:Serotonin / Q000494:pharmacology / Q000502:physiology*; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000378:metabolism; D053773:Transforming Growth Factor beta1 / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D015854:Up-Regulation
D024042:Collagen Type I; D000090602:Collagen Type I, alpha 1 Chain; D015850:Interleukin-6; C560825:Timp1 protein, mouse; D019715:Tissue Inhibitor of Metalloproteinase-1; D053773:Transforming Growth Factor beta1; D014409:Tumor Necrosis Factor-alpha; C577686:interleukin-6, mouse; D012701:Serotonin; D020778:Matrix Metalloproteinase 2; C522362:Mmp2 protein, mouse
Fibrosis; inflammation; proximal tubular epithelial cells; renal injury; serotonin