Pannexin1: insight into inflammatory conditions and its potential involvement in multiple organ dysfunction syndrome

Abstract

Sepsis represents a global health concern, and patients with severe sepsis are at risk of experiencing MODS (multiple organ dysfunction syndrome), which is associated with elevated mortality rates and a poorer prognosis. The development of sepsis involves hyperactive inflammation, immune disorder, and disrupted microcirculation. It is crucial to identify targets within these processes to develop therapeutic interventions. One such potential target is Panx1 (pannexin-1), a widely expressed transmembrane protein that facilitates the passage of molecules smaller than 1 KDa, such as ATP. Accumulating evidence has implicated the involvement of Panx1 in sepsis-associated MODS. It attracts immune cells via the purinergic signaling pathway, mediates immune responses via the Panx1-IL-33 axis, promotes immune cell apoptosis, regulates blood flow by modulating VSMCs’ and vascular endothelial cells’ tension, and disrupts microcirculation by elevating endothelial permeability and promoting microthrombosis. At the level of organs, Panx1 contributes to inflammatory injury in multiple organs. Panx1 primarily exacerbates injury and hinders recovery, making it a potential target for sepsis-induced MODS. While no drugs have been developed explicitly against Panx1, some compounds that inhibit Panx1 hemichannels have been used extensively in experiments. However, given that Panx1’s role may vary during different phases of sepsis, more investigations are required before interventions against Panx1 can be applied in clinical. Overall, Panx1 may be a promising target for sepsis-induced MODS. Nevertheless, further research is needed to understand its complex role in different stages of sepsis fully and to develop suitable pharmaceutical interventions for clinical use.

Pannexins in the musculoskeletal system: new targets for development and disease progression

“… 178 In addition, there are many reagents that inhibit the channels formed by Panxs and Cxs, but more inhibitory mechanisms have yet to be explored. 179 , 180 …”

“…178 In addition, there are many reagents that inhibit the channels formed by Panxs and Cxs, but more inhibitory mechanisms have yet to be explored. 179,180 In various diseases, targeting Cxs has proven to be an effective therapeutic approach by either permanently or temporarily closing the channels. This strategy holds great potential for systematic research and targeted therapy of Panxs in the future.…”

Elucidating VSMC phenotypic transition mechanisms to bridge insights into cardiovascular disease implications

“…The release of MMPs by transformed VSMCs in AAA leads to the accelerated breakdown of the extracellular matrix ( 109 ), and similar mechanisms are observed in AD where altered VSMC phenotype contributes to the progression of the dissection ( 106 ). Additionally, the involvement of specific pathways like the pannexin-1 (Panx-1)/P2Y2 receptor pathway in VSMC activation indicates shared molecular targets that could be explored for therapeutic interventions in both conditions ( 110 ).…”

The emerging role of Panx1 as a potential therapeutic target for chronic pain

“…Xing et al [ 3 ] provide promising insights into how Panx1 facilitates inflammatory pain through experiments on pain sensitivity and neuronal excitability. Few studies have demonstrated the translational progress of Panx1 as the target for inflammation and disease control [ 11 – 13 ], so further research characterizing the interactions of pharmacological treatments on Panx1, the Wnt/β-catenin signaling pathway, and DRG may elucidate promising avenues for the treatment of chronic pain in the military population.…”