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Nat Commun. 2018 Dec 3;9(1):5129. doi: 10.1038/s41467-018-07638-4.

Islr regulates canonical Wnt signaling-mediated skeletal muscle regeneration by stabilizing Dishevelled-2 and preventing autophagy.

Author information

1
State Key Laboratories for Agrobiotechnology, College of Biological Sciences, China Agricultural University, Yuanmingyuan West Road No. 2, Haidian District, Beijing, 100193, China.
2
Beijing Advanced Innovation Center for Food Nutrition and Human Health, College of Biological Sciences, China Agricultural University, Yuanmingyuan West Road No. 2, Haidian District, Beijing, 100193, China.
3
Beijing Advanced Innovation Center for Food Nutrition and Human Health, College of Food Science & Nutritional Engineering, China Agricultural University, Yuanmingyuan West Road No. 2, Haidian District, Beijing, 100193, China.
4
State Key Laboratories for Agrobiotechnology, College of Biological Sciences, China Agricultural University, Yuanmingyuan West Road No. 2, Haidian District, Beijing, 100193, China. qingyong.meng@gmail.com.
5
Beijing Advanced Innovation Center for Food Nutrition and Human Health, College of Biological Sciences, China Agricultural University, Yuanmingyuan West Road No. 2, Haidian District, Beijing, 100193, China. qingyong.meng@gmail.com.

Abstract

Satellite cells are crucial for skeletal muscle regeneration, but the molecular mechanisms regulating satellite cells are not entirely understood. Here, we show that the immunoglobulin superfamily containing leucine-rich repeat (Islr), a newly identified marker for mesenchymal stem cells, stabilizes canonical Wnt signaling and promote skeletal muscle regeneration. Loss of Islr delays skeletal muscle regeneration in adult mice. In the absence of Islr, myoblasts fail to develop into mature myotubes due to defective differentiation. Islr interacts with Dishevelled-2 (Dvl2) to activate canonical Wnt signaling, consequently regulating the myogenic factor myogenin (MyoG). Furthermore, Islr stabilizes Dvl2 by reducing the level of LC3-labeled Dvl2 and preventing cells from undergoing autophagy. Together, our findings identify Islr as an important regulator for skeletal muscle regeneration.

PMID:
30510196
PMCID:
PMC6277414
DOI:
10.1038/s41467-018-07638-4
[Indexed for MEDLINE]
Free PMC Article

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