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Prostaglandin E 2 Signaling via EP4 Receptor is Important for Cell Cycle Progression and the Regulation of Reactive Oxygen Species Production in Primary Myoblast
Author(s) -
Mo Chenglin,
Wetmore Lori,
Zhao Ruonan,
Bonewald Lynda,
Brotto Marco
Publication year - 2015
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.29.1_supplement.947.16
Subject(s) - myogenesis , downregulation and upregulation , reactive oxygen species , microbiology and biotechnology , cell growth , chemistry , signal transduction , receptor , endocrinology , medicine , myocyte , biology , biochemistry , gene
Our previous data have shown that conditioned media from osteocytes and prostaglandin E 2 (PGE 2 ), a major secreted factor by osteocytes, promotes C2C12 myogenesis. PGE 2 and EP4 receptor agonist CAY10598 enhance, but EP4 receptor antagonist L161,982 inhibits primary myoblast proliferation. Since the activation of other EP receptors did not show any noticeable effect, EP4 receptor may play a major role in the regulation of primary myoblast proliferation. To further study the mechanisms behind these effects of PGE 2 /EP4 signaling, we determined the gene expression of cell cycle regulators, such as cyclin E, p21, and myostatin, following the treatments with PGE 2 , CAY10598 or L161,982. Consistent with our findings in cell cycle analysis, the results indicated that PGE 2 and CAY 10598 upregulate cylin E expression, but downregulate p21 and myostatin expression. In contrast, L161,982 decreases cylin E expression, but increases p21 and myostatin expression. Moreover, treatment with L161,982 significantly increased reactive oxygen species (ROS) levels by 250%. Cotreatment with antioxidant N‐acetyl cysteine or sodium ascorbate successfully reverses the inhibition of myoblast proliferation and excessive ROS production caused by L161,982. These results suggest that PGE 2 signaling via EP4 receptor could regulate myogenesis by promoting myoblast proliferation via a ROS‐dependent modulation of cell cycle.