Muscle composition is regulated by a Lox-TGF beta feedback loop

作者:Kutchuk Liora; Laitala Anu; Soueid Bomgarten Sharon; Shentzer Pessia; Rosendahl Ann Helen; Eilot Shelly; Grossman Moran; Sagi Irit; Sormunen Raija; Myllyharju Johanna; Maki Joni M; Hasson Peleg*
来源:Development, 2015, 142(5): 983-993.
DOI:10.1242/dev.113449

摘要

Muscle is an integrated tissue composed of distinct cell types and extracellular matrix. While much emphasis has been placed on the factors required for the specification of the cells that comprise muscle, little is known about the crosstalk between them that enables the development of a patterned and functional tissue. We find in mice that deletion of lysyl oxidase (Lox), an extracellular enzyme regulating collagen maturation and organization, uncouples the balance between the amount of myofibers and that of muscle connective tissue (MCT). We show that Lox secreted from the myofibers attenuates TGF beta signaling, an inhibitor of myofiber differentiation and promoter of MCT development. We further demonstrate that a TGF beta-Lox feedback loop between the MCT and myofibers maintains the dynamic developmental homeostasis between muscle components while also regulating MCT organization. Our results allow a better understanding of diseases such as Duchenne muscular dystrophy, in which LOX and TGF beta signaling have been implicated and the balance between muscle constituents is disturbed.

  • 出版日期2015-3-1