Involvement of natriuretic peptide system in C2C12 myocytes
The natriuretic peptide system, a key regulator of cGMP signaling, comprises three types of natriuretic peptides, osteocrin/musclin (OSTN), and their natriuretic peptide receptors. Although this system plays important roles in many organs, its physiological roles in skeletal muscle have not been clearly described. In the present study, we investigated the role of the natriuretic peptide system in C2C12 myocytes. All three natriuretic peptide receptors were expressed by cells differentiating from myoblasts to myotubes, and natriuretic peptide receptor B (NPR-B) transcripts were detected at the highest levels. Further, higher levels of cGMP were generated in response to stimulation with C-type natriuretic peptide (CNP) versus atrial natriuretic peptide (ANP), which reflected receptor expression levels. A cGMP analog downregulated the expression of a few ER stress-related genes. Furthermore, OSTN gene expression was strongly upregulated after 20 days of differentiation. Augmented gene expression was found to correlate closely with endoplasmic reticulum (ER) stress, and C/EBP [CCAAT-enhancer-binding protein] homologous protein (CHOP), which is known to be activated by ER stress, affected the expression of OSTN. Together, these results suggest a role for natriuretic peptide signaling in the ER stress response of myocytes.
KeywordsNatriuretic peptide Cyclic GMP ER stress Skeletal muscle Cell signaling
Atrial natriuretic peptide
Activating transcription factor
Brain natriuretic peptide
C/EBP homologous protein
C-type natriuretic peptide
Myosin heavy chain
Myogenic factor 5
Natriuretic peptide receptor A
Natriuretic peptide receptor B
Natriuretic peptide receptor C
PKR-like ER kinase
Unfolded protein response
X-box binding protein 1
We thank Shinji Kojima of the Mitsubishi Tanabe Pharma Corporation, Japan, for his technical assistance. This work was partly supported by Mitsubishi Tanabe Pharma Corporation, Japan. The authors would like to thank Enago (http://www.enago.jp) for the English language review.
Compliance with ethical standards
Conflict of interest
The authors declare that they have no conflicts of interest with the contents of this article.
All procedures performed in studies involving animals were in accordance with the ethical standards of the institution or practice at which the studies were conducted.
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