Poster Session III. - P: Health Sciences
Fazekas László
Department of Physiology
László Fazekas1,2,3, Diána Kaszás1,2,3, Szimonetta Xénia Tamás1,2,3, Boldizsár Vámosi1,3, Al-Sheraji Nada Mohamed1,3, Tamás Szöllősi1, Vivien Mihályi1, Paulovits Barnabás1, Fabian Gregor Dehne1,2,3, Klaudia Vágó-Kiss1,2,3, Benoit Thomas Roux1,3, Balázs Enyedi1,2,3
1: Department of Physiology, Semmelweis University, Faculty of Medicine, Tűzoltó utca 37-47, H-1094, 7 Budapest, Hungary
2: MTA-SE Lendület Tissue Damage Research Group, Hungarian Academy of Sciences and Semmelweis 9 University, H-1094 Budapest, Hungary
3: HCEMM-SE Inflammatory Signaling Research Group, Department of Physiology, Semmelweis University, 11 H-1094 Budapest, Hungary
Effective wound healing depends on the coordinated action of multiple cell types, including fibroblasts, which are key players in tissue remodeling during the later stages of repair. However, studying fibroblast function in zebrafish has been hampered by the lack of robust, cell-type-specific genetic tools.
Here, we developed a novel fibroblast-specific promoter by combining the zebrafish integrin α11a (itga11a) promoter with the murine cFos minimal promoter. Establishing this itga11a-cFos promoter in the QF2-QUAS binary expression system allowed us to evaluate tissue-damage induced signaling pathways in fibroblasts using genetically encoded biosensors.
By expressing the GCaMP7s calcium sensor in fibroblasts we identified distinct Ca²⁺ signaling events triggered by injury and hypotonic conditions. In response to tissue damage, we observed that subcutaneous fibroblasts also actively respond to osmotic changes, displaying significantly different calcium signaling patterns compared to epithelial cells. Unlike epithelial cells, which display rapid, oscillatory calcium transients, fibroblasts respond with sustained intracellular calcium elevations, suggesting different functional roles in the wound response. While epithelial cells may initiate immediate repair mechanisms, fibroblasts likely integrate signals over longer timescales to regulate gene expression and tissue remodeling.
Furthermore, we also show that tissue damage results in the activation of the cPla2-mediated shape-sensing and nuclear swelling dependent pathway in fibroblasts.
Together, our results establish Tg(itga11a-cFos:QF2) as a powerful tool for fibroblast-specific manipulation and imaging in vivo, enabling new insights into the roles of fibroblasts during tissue damage and repair.
This research was supported by New National Excellence Program of the Ministry for Culture and Innovation of Hungary from the source of the National Research, Development and Innovation Fund (EKÖP-2024-267).