The role of pannexin hemichannels in inﬂammation and regeneration

Frontiers in Physiology, 2014 · DOI: 10.3389/fphys.2014.00063 · Published: February 25, 2014

Simple Explanation

Tissue injury triggers systemic responses like inflammation, cell migration, and stem cell activation. Communication between cells during regeneration relies on ATP, released via hemichannels made of connexins and pannexins. Pannexins are proteins that form hemichannels in cell membranes, facilitating the exchange of molecules like ATP. Panx1, a key pannexin, is involved in purinergic signaling and ATP release, with its activity increasing after injury or inflammation. Pannexins play roles in both the post-injury inflammatory response and tissue regeneration. Because of their wide expression and involvement in signaling pathways, they are potential therapeutic targets for injuries and diseases.

Study Duration

Not specified

Participants

Not specified

Evidence Level

Review Article

Key Findings

1
Pannexin-1 (Panx1) channels function as an integral component of the P2X/P2Y purinergic signaling pathway and is arguably the major contributor to pathophysiological ATP release.
2
Pharmacological blockade of the Panx1 channel or genetic ablation of the Panx1 gene cause signiﬁcant disruption of progenitor cell migration, proliferation, and tissue regeneration.
3
Pannexin hemichannels might serve as primary sensors of cell micro-environmental changes that allow cells within a tissue to respond proactively to environmental stresses.

Research Summary

This review focuses on the role pannexins play in inflammation-induced regeneration in various tissues, highlighting their involvement in cell death, differentiation, and tissue repair. Pannexins, particularly Panx1, mediate ATP release, which is a key step in inflammatory responses. This ATP release activates purinergic receptors and promotes the maturation of inflammatory cytokines. The review also discusses the role of connexin hemichannels in inflammation and regeneration, noting that while they share similarities with pannexins, they have distinct physiological properties and may be critical to maintain the stress response.

Practical Implications

Therapeutic Targets

Pannexins, due to their involvement in multiple cellular functions and wide expression, represent potential therapeutic targets for immune disorders, cancer, and acute inflammation.

Wound Healing Enhancement

Understanding the role of pannexins in progenitor cell proliferation, migration, and differentiation may lead to strategies for enhancing wound healing and regeneration.

Context-Dependent Targeting

Defining the distinct roles of pannexin hemichannels in different physiological processes allows for the possibility of targeting these channels and ATP release in a context-dependent manner.

Study Limitations

1
The precise role of pannexins in the balance between tissue inflammation and regeneration needs to be further understood.
2
The diversity of the cell states in this diseases suggests that Panx1 function in cellular processes leading to chronic inﬂammation, cell death, and disease that remain to be fully deﬁned.
3
The mechanism of delayed opening of connexin hemichannels is not yet clear.

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