PhD Scientific Days 2025

Poster Session II. - B: Molecular Medicine

Spatiotemporal Patterns of Calcium and ATP Signaling in Wound Response

Name of the presenter

Kaszás Diána

Institute/workplace of the presenter

SE, Department of physiology

Authors

Diána Kaszás¹, Dr. Balázs Enyedi¹, László Fazekas¹, Benoit Roux¹

1: SE, Department of physiology

Text of the abstract

Wound healing is a dynamic and complex physiological process that begins immediately after tissue injury. It involves the rapid release of regulatory molecules and the activation of key signaling pathways essential for tissue repair. Our study focuses on two critical components of these mechanisms: extracellular ATP (eATP) secretion, a well-known damage-associated molecular pattern (DAMP), and intracellular Ca²⁺ signaling, both of which are rapidly triggered upon wounding. Previous research has established that these signals emerge almost instantaneously, with eATP acting as a "danger signal" via purinergic receptors, while localized Ca²⁺ influx initiates key downstream processes. These signals are crucial for immune cell recruitment and the activation of early gene transcription necessary for cell proliferation and migration. However, the mechanisms underlying the distinct spatiotemporal patterns of Ca²⁺ signaling remain unclear.
Using transgenic zebrafish lines expressing GRABATP and GCaMP7s sensors, we were able to detect both passive ATP release from wounded cells and active ATP secretion. Our Ca²⁺ sensor line revealed three distinct signaling patterns: (1) a persistent high Ca²⁺ signal near the wound edge, (2) a wave propagating deeper into the tissue, and (3) oscillatory Ca²⁺ signaling in epithelial cells further from the wound. These signals appeared nearly simultaneously and spread across hundreds of micrometers within seconds. While we initially attributed their propagation to diffusion, our data suggest a faster underlying mechanism. To better understand this process, we are collaborating with Prof. Tamás Vicsek’s physics group to develop a mathematical model describing these early wound responses.
Additionally, our findings indicate that strong Ca²⁺ oscillations and eATP release can also be triggered by significant tissue movement, even in the absence of injury. A similar pattern emerges minutes after wounding, suggesting that these signals may be driven by immediate wound contraction and subsequent cell movement.
Moving forward, in collaboration with Prof. Tamás Vicsek, we aim to develop a mathematical model describing the immediate appearance of Ca²⁺ and ATP signals following injury. Additionally, our measurements seek to identify the mechanoreceptor responsible for Ca²⁺ oscillations and active ATP release triggered by tissue movement.