Ca2+ signaling in chronic rhinosinusitis with nasal polyps: Deciphering mechanistic insights and future therapeutic targets.
Kalaji Zaina Z, Hamadi Iyad Said IS, Al-Waa Ahmad Munzer AM, Hamoudi Rifat R et al.
Chronic rhinosinusitis with nasal polyps (CRSwNP) is a prevalent yet inadequately understood condition characterized by benign lesions originating from inflamed nasal sinuses. It impacts patients by inducing nasal obstruction, inflammation, and recurrent symptoms. The pathophysiological mechanisms underlying nasal polyposis are not fully elucidated, which constrains the efficacy of current therapeutic interventions such as intranasal corticosteroids (INCSs), functional endoscopic sinus surgery (FESS), and biologics, particularly in severe, treatment-resistant, or recurrent cases. Recent research indicates that calcium (Ca2+) channels, notably with the use of blockers like Verapamil, may provide therapeutic benefits by addressing these challenges, demonstrating promising outcomes without significant adverse effects. Nonetheless, the molecular mechanisms involving Ca2+-dependent signaling pathways in CRSwNP remain insufficiently characterized, with a paucity of studies examining their dysregulation and contribution to disease pathology. Consequently, identifying critical components involved in disruptions of Ca2+ signaling is of paramount importance. We aim to encourage further research into the role of Ca2+ signaling in nasal polyposis and to identify potential pathways and novel targets for innovative treatments. This review consolidates current knowledge concerning Ca2+ signaling in CRSwNP, highlighting the roles of various Ca2+ channels and their downstream signaling cascades in modulating key pathological and clinical outcomes that are uniquely characteristic of the disease. Furthermore, we provide novel in silico insights into the potential pathogenic role of KCa3.1 through its interactions with genes such as TRPM6, EGF, HRH1, BCL2A1, and CD209 in CRSwNP, an area that has not been previously examined. This implicates new components and explores potential targets for future therapeutic strategies.