Exp Mol Med.  2009 May;41(5):307-314. 10.3858/emm.2009.41.5.034.

Calcitonin induces connective tissue growth factor through ERK1/2 signaling in renal tubular cells

• Nakamura M
• Ozaki T
• Ishii A
• Konishi M
• Tsubota Y
• Furui T
• Tsuda H
• Mori I
• Ota K
• Kakudo K

• KMID: 1123804
• DOI: http://doi.org/10.3858/emm.2009.41.5.034

Abstract

Calcitonin (CT), a polypeptide hormone, plays important roles in a variety of physiological processes. CT has been used clinically to treat osteoporosis and humoral hypercalcemia of malignancy. In order to clarify the pharmacological effects of CT in the kidney, we identified potential downstream genes induced by CT in the renal cells. Using a cDNA subtraction hybridization method, we identified connective tissue growth factor (CTGF) as a CT-induced gene in the porcine renal cell line, LLC-PK1. Furthermore, we found that CT-mediated induction of the gene was not inhibited by cycloheximide, which suggests that CTGF gene was not induced by an increased synthesis of regulating proteins. Therefore, CTGF is an immediate early gene. We further demonstrated that the regulation of CTGF gene expression by CT involved the ERK1/2 pathway, because PD98059, a MEK1 inhibitor, partially inhibited the mRNA expression of CTGF induced by CT. CT-induced CTGF protein expression was also observed in vivo. Our present findings suggest that CT induces the transcription of CTGF through ERK1/2 phosphorylation. We also identified twelve other genes induced by CT that, like CTGF, were related to wound healing. These results suggest that CT may have an effect on renal differentiation and wound healing in the kidney.

Keyword

calcitonin; connective tissue growth factor; extracellular signal-regulated MAP kinases; gene expression regulation; kidney; wound healing

MeSH Terms

Animals
Calcitonin/*pharmacology
Cell Line
Connective Tissue Growth Factor/*genetics/metabolism
Female
Kidney Tubules, Proximal/*enzymology/metabolism
*MAP Kinase Signaling System
Mice
Mice, Inbred BALB C
Mitogen-Activated Protein Kinase 1/*metabolism
Mitogen-Activated Protein Kinase 3/*metabolism
Phosphorylation
Swine