Expression of Pannexin 1 and Pannexin 3 during skeletal muscle development, regeneration, and Duchenne muscular dystrophy

Abstract

Pannexin 1 (Panx1) and Pannexin 3 (Panx3) are single membrane channels recently implicated in myogenic commitment, as well as myoblast proliferation and differentiation in vitro. However, their expression patterns during skeletal muscle development and regeneration had yet to be investigated. Here, we show that Panx1 levels increase during skeletal muscle development becoming highly expressed together with Panx3 in adult skeletal muscle. In adult mice, Panx1 and Panx3 were differentially expressed in fast- and slow-twitch muscles. We also report that Panx1/PANX1 and Panx3/PANX3 are co-expressed in mouse and human satellite cells, which play crucial roles in skeletal muscle regeneration. Interestingly, Panx1 and Panx3 levels were modulated in muscle degeneration/regeneration, similar to the pattern seen during skeletal muscle development. As Duchenne muscular dystrophy is characterized by skeletal muscle degeneration and impaired regeneration, we next used mild and severe mouse models of this disease and found a significant dysregulation of Panx1 and Panx3 levels in dystrophic skeletal muscles. Together, our results are the first demonstration that Panx1 and Panx3 are differentially expressed amongst skeletal muscle types with their levels being highly modulated during skeletal muscle development, regeneration, and dystrophy. These findings suggest that Panx1 and Panx3 channels may play important and distinct roles in healthy and diseased skeletal muscles.

Identification of pannexin 1-regulated genes, interactome, and pathways in rhabdomyosarcoma and its tumor inhibitory interaction with AHNAK

“…Pannexins (PANX1, PANX2, and PANX3) are single membrane channels that allow the release of small molecules such as nucleotides [8]. Our work has shown that PANX1 levels are low in undifferentiated skeletal muscle myoblasts and increase during myogenesis in vitro and in vivo [6,9]. Blocking PANX1 channel activity inhibited myoblast differentiation, while PANX1 overexpression promoted this process [6].…”

eATP/P2X7R Axis: An Orchestrated Pathway Triggering Inflammasome Activation in Muscle Diseases

“…Pannexin hemichannels were reported to mediate ATP release upon electrical stimulation [ 92 , 93 ], mechanical stress, and elevated extracellular potassium ion concentration [ 94 ]. Pannexin (PANX) 1 and 3 are expressed by myoblasts and SCs and are involved in the regulation of myoblast proliferation, differentiation and skeletal muscle development [ 92 , 95 , 96 ]. PANX1 levels are dramatically induced during myoblast differentiation, whereas PANX3 is mainly expressed in differentiated human skeletal muscle tissue, and its over-expression inhibits myoblast proliferation and induces their differentiation [ 95 , 96 ].…”

“…In addition, PANX1 regulates the oxidative state during exercise [ 100 ]. PANX3 has also been demonstrated to mediate eATP release [ 101 ], likely being involved in contraction and metabolism [ 96 ].…”

“…In mdx mice PANX1 and PANX3 levels are dysregulated, even though in different ways depending on the muscle type [ 96 ]. ThePANX3 role in DMD is still to be fully characterized: it has been suggested that PANX3-mediated ATP release may contribute to attraction of monocytes, which may enhance muscle inflammation [ 94 ].…”

Pannexin 1 Influences Lineage Specification of Human iPSCs

“…In healthy cells PANX1 channels normally remain in a closed state until induced to transiently open in response to a variety of stimuli including membrane deformation, receptor activation, and intracellular calcium release (Sandilos et al, 2012;Bao et al, 2013;Furlow et al, 2015;Sanchez-Arias et al, 2019). PANX1 signaling can also influence the self-renewal and differentiation of multiple somatic (adult) stem cell types including osteoprogenitor cells, skeletal myoblasts, and postnatal neural precursor cells (Wicki-Stordeur et al, 2012;Wicki-Stordeur and Swayne, 2013;Wicki-Stordeur et al, 2016;Ishikawa and Yamada, 2017;Pham et al, 2018). However, much less is known about the impact of PANX1 signaling in the early embryo or in pluripotent stem cells (Hainz et al, 2018).…”