The Preliminary Study On UPR Signaling Pathway Participating In The Expression Of Musclin Induced By Palmitate

Musclin is a kind of secretion factor coming from skeletal muscle, and its m RNA expression almost exclusively exist in skeletal muscle with high tissue specificity. Studies have shown that Musclin highly expressed in patients with type Ⅱ diabetes, which may be related to the glucose and lipid metabolism disorder in the body. Glucose and lipid metabolic disorder is always associated with an increase of free fatty acids in the blood, whose main constituent is palmitic acid, and it was speculated that palmitic acid may induce the expression of musclin gene. Therefore, in the early study palmitic acid was taken to deal with the differentiated C2C12 myoblast. The results showed that the expression of musclin gene highly increased with the existence of palmitic acid. In addition, there exists a positive correlation between the expression of musclin gene and ER-related genes. At present, it is still not clear that what role each UPR signaling pathway plays in the expression of musclin gene induced by the palmitate.Based on the issues above, this study respectively do a preliminary research about the three ER stress pathways: PERK, IRE1 and ATF6 signaling pathways. Inhibitors and sh-RNA technique were used to inhibit and block the pathways which were detected through related molecular detection by q RT-PCR and Western Blot. On above foundation the expression of musclin gene was detected by q RT-PCR to explore whether the three pathways were involved in the expression of musclin gene induced by palmitic acid.The results show that the expression of musclin gene induced by palmitate is accordingly inhibited after PERK signaling pathway is inhibited or blocked, which can preliminarily prove that PERK signaling pathway involves in the musclin expression induced by palmitate; However, with IRE1 or ATF6 signaling pathway being suppressed or blocked, the expression of musclin gene induced by palmitate isn’t significantly influenced, suggesting that IRE1 and ATF6 signaling pathways don’t participate in the expression. This result of study provides a new thought for researching metabolic diseases such as diabetes.