Calcium signaling pathway in epithelial cells

The calcium signaling pathway in epithelial cells is a complex network of ion channels, pumps, and receptors that regulate the concentration of cytosolic calcium ions (Ca2+) to mediate various cellular processes [2, 11]. In epithelial tissues, such as those in the lungs, gut, and skin, calcium acts as a critical second messenger for functions including ion secretion, mucociliary clearance, and wound healing [7, 14]. Dysregulation of this pathway is a hallmark of several pathologies, including inflammatory airway diseases like asthma and COPD, where it drives cytokine release and mucus hypersecretion [4, 8]. In oncology, remodeled calcium signaling promotes epithelial-mesenchymal transition (EMT), enhancing tumor cell motility, invasion, and resistance to therapy [5, 6]. Therapeutic strategies often focus on specific components of the pathway, such as store-operated calcium entry (SOCE) mediated by Orai1 and STIM1, or various transient receptor potential (TRP) channels [3, 9]. However, the ubiquitous nature of calcium signaling poses significant challenges for drug development, requiring high specificity to avoid systemic side effects [10, 11]. This pathway integrates multiple extracellular signals, including mechanical stress and chemical ligands, to coordinate tissue-level responses [10, 12]. Understanding the cell-specific calcium toolkit is essential for developing targeted therapies that can correct derailed signaling without disrupting global homeostasis [2, 9].

Other names

Epithelial calcium signalingIntracellular calcium signaling in epitheliumCalcium signaling toolkit in epithelial cells

Modulation of cytosolic calcium concentrations through the regulation of ion channels (e.g., Orai, TRP), pumps (e.g., SERCA, PMCA), and receptors (e.g., IP3R, RyR) to control downstream signaling cascades and cellular responses.