Interleukin-15 facilitates muscle regeneration through modulation of fibro/adipogenic progenitors.

Autor: Kang X; Department of Orthopedic Surgery, Southwest Hospital, Third Military Medical University, Gaotanyan Str. 30, Chongqing city, 400038, People's Republic of China., Yang MY; Department of Orthopedic Surgery, Southwest Hospital, Third Military Medical University, Gaotanyan Str. 30, Chongqing city, 400038, People's Republic of China., Shi YX; Department of Orthopedic Surgery, Southwest Hospital, Third Military Medical University, Gaotanyan Str. 30, Chongqing city, 400038, People's Republic of China., Xie MM; Department of Orthopedic Surgery, Southwest Hospital, Third Military Medical University, Gaotanyan Str. 30, Chongqing city, 400038, People's Republic of China., Zhu M; Department of Orthopedic Surgery, Southwest Hospital, Third Military Medical University, Gaotanyan Str. 30, Chongqing city, 400038, People's Republic of China., Zheng XL; Department of Orthopedic Surgery, Southwest Hospital, Third Military Medical University, Gaotanyan Str. 30, Chongqing city, 400038, People's Republic of China., Zhang CK; Department of Orthopedic Surgery, Southwest Hospital, Third Military Medical University, Gaotanyan Str. 30, Chongqing city, 400038, People's Republic of China., Ge ZL; Department of Orthopedic Surgery, Southwest Hospital, Third Military Medical University, Gaotanyan Str. 30, Chongqing city, 400038, People's Republic of China., Bian XT; Department of Orthopedic Surgery, Southwest Hospital, Third Military Medical University, Gaotanyan Str. 30, Chongqing city, 400038, People's Republic of China., Lv JT; Department of Orthopedic Surgery, Southwest Hospital, Third Military Medical University, Gaotanyan Str. 30, Chongqing city, 400038, People's Republic of China., Wang YJ; Department of Orthopedic Surgery, Southwest Hospital, Third Military Medical University, Gaotanyan Str. 30, Chongqing city, 400038, People's Republic of China., Zhou BH; Department of Orthopedic Surgery, Southwest Hospital, Third Military Medical University, Gaotanyan Str. 30, Chongqing city, 400038, People's Republic of China. yijian510868@hotmail.com., Tang KL; Department of Orthopedic Surgery, Southwest Hospital, Third Military Medical University, Gaotanyan Str. 30, Chongqing city, 400038, People's Republic of China. tangkanglai@hotmail.com.
Jazyk: angličtina
Zdroj: Cell communication and signaling : CCS [Cell Commun Signal] 2018 Jul 20; Vol. 16 (1), pp. 42. Date of Electronic Publication: 2018 Jul 20.
DOI: 10.1186/s12964-018-0251-0
Abstrakt: Background: Chronic muscle injury is characteristics of fatty infiltration and fibrosis. Recently, fibro/adipogenic progenitors (FAPs) were found to be indispensable for muscular regeneration while were also responsible for fibrosis and fatty infiltration in muscle injury. Many myokines have been proven to regulate the adipose or cell proliferation. Because the fate of FAPs is largely dependent on microenvironment and the regulation of myokines on FAPs is still unclear. We screened the potential myokines and found Interleukin-15 (IL-15) may regulate the fatty infiltration in muscle injury. In this study, we investigated how IL-15 regulated FAPs in muscle injury and the effect on muscle regeneration.
Methods: Cell proliferation assay, western blots, qRT-PCR, immunohistochemistry, flow cytometric analysis were performed to investigate the effect of IL-15 on proliferation and adipogensis of FAPs. Acute muscle injury was induced by injection of glycerol or cardiotoxin to analyze how IL-15 effected on FAPs in vivo and its function on fatty infiltration or muscle regeneration.
Results: We identified that the expression of IL-15 in injured muscle was negatively associated with fatty infiltration. IL-15 can stimulate the proliferation of FAPs and prevent the adipogenesis of FAPs in vitro and in vivo. The growth of FAPs caused by IL-15 was mediated through JAK-STAT pathway. In addition, desert hedgehog pathway may participate in IL-15 inhibiting adipogenesis of FAPs. Our study showed IL-15 can cause the fibrosis after muscle damage and promote the myofiber regeneration. Finally, the expression of IL-15 was positively associated with severity of fibrosis and number of FAPs in patients with chronic rotator cuff tear.
Conclusions: These findings supported the potential role of IL-15 as a modulator on fate of FAPs in injured muscle and as a novel therapy for chronic muscle injury.
Databáze: MEDLINE
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