UDPG/P2Y₁₄-STAT1 axis mediates LPS-induced reactive astrogliosis

Area of Science:

• Neuroscience
• Immunology
• Cell Biology

Background:

• Astrocytes are crucial in central nervous system (CNS) neuroinflammation.
• Purinergic G protein-coupled receptor P2Y14 is implicated in neuroinflammation, but its role in astrocytes is unclear.
• Understanding astrocyte P2Y14 function is vital for neuroinflammatory research.

Purpose of the Study:

• To investigate P2Y14 receptor expression and distribution in astrocytes.
• To elucidate the regulatory role of P2Y14 in astrocytic inflammatory responses.
• To explore the underlying molecular mechanisms involving the UDPG/P2Y14-STAT1 signaling axis.

Main Methods:

• Primary mouse astrocytes and C8-D1A cell line were used.
• Immunofluorescence, Western blot, and RT-qPCR confirmed P2Y14 expression.
• Pharmacological agents (PPTN, UDPG) and lentiviral transduction modulated P2Y14 activity and expression.

Main Results:

• P2Y14 receptors are expressed in astrocytes and their expression increases upon LPS stimulation.
• P2Y14 activation by UDPG promotes astrocyte activation (GFAP expression) and inflammatory mediator release (IL-6, IL-18, TNF-α).
• P2Y14 antagonist PPTN inhibits GFAP expression and inflammatory cytokine release, partly via the STAT1/p-STAT1 pathway.

Conclusions:

• Astrocytes express functional P2Y14 receptors that play a key role in neuroinflammation.
• The UDPG/P2Y14-STAT1 signaling pathway is a critical regulator of astrocytic inflammatory responses.
• P2Y14 represents a potential therapeutic target for CNS inflammatory diseases.