Progranulin down-regulates miR-206 to promote myogenic progenitor cells proliferation in muscle development

• Main Authors: Chum-Miao Hsu, 許淳淼
• Other Authors: 吳金洌
• Format: Others
• Language: en_US
• Published: 2015
• Online Access: http://ndltd.ncl.edu.tw/handle/83432017751870622329

碩士 === 國立臺灣大學 === 漁業科學研究所 === 103 === Progranulin (PGRN) is a secreted growth factor that contribute to early embryogenesis, wound healing response and tumorigenesis. In our previous research, the transgenic zebrafish Tg(mlc2:grnA) overexpressing zebrafish progranulinA (GrnA) in musce showed that PGRN promotes muscle growth. But the mechanism how PGRN promotes muscle growth is still elusive. Previous research also showed that knockdown of GrnA resulted in impaired muscle growth and reduced quantity of Pax7+ myogenic progenitor cells (MPCs). Yet the reduced quantity of MPCs could be restored by ectopic expression of MET, the receptor for HGF. Hence, the relationship between PGRN, MET and Pax7+ MPCs may play a critical role in promoting muscle growth. On the other hand, some studies have identified that muscle specific microRNA (miRNA) participate in myogenesis and muscle growth. MiR-206 is one of muscle specific miRNA, that targets MET, Pax7 and inhibit MPCs proliferation. Additionally, premiere results revealed that miR-206 might be a downstream factor of PGRN. Here, we hypothesized that PGRN might down-regulate miR-206 to modulate MET, Pax7 expression and promote MPCs proliferation. Then the proliferation of MPCs provides more cells differentiating into myotube and promotes muscle growth. In this study, we demonstrated that overexpressing PGRN in C2C12 cells promotes cells proliferation. And the downstream factor, MET and Pax7 were up-regulated, but miR-206 was down-regulated. In contrast, knockdown of PGRN in C2C12 cells showed converse results in MET, Pax7 and miR-206 expression. And the reduced expression of MET and Pax7 caused by knocking down of PGRN can be rescued by inhibiting miR-206 expression. Moreover, in the zebrafish system, miR-206 was down-regulated in Tg(mlc2:grnA) at 24 and 48 hpf. Tg(mlc2:grnA) also showed increased MPCs at 24 hpf. And these increased MPCs resulted from enhanced proliferation of MPCs. As expected, the nucleus number in the somite was increased in Tg(mlc2:grnA) at 6 dpf. Additionally, Tg(mlc2:grnA) showed higher body weight compare to WT zebrafish. Based on these finding, PGRN/miR-206 axis plays an important role in muscle growth. And in the future, we will apply these findings to further muscle growth and aquaculture research.