Transient Receptor Potential Channels and Chronic Airway Inflammatory Diseases: A Comprehensive Review

Abstract

Chronic airway inflammatory diseases remain a major problem worldwide, such that there is a need for additional therapeutic targets and novel drugs. Transient receptor potential (TRP) channels are a group of non-selective cation channels expressed throughout the body that are regulated by various stimuli. TRP channels have been identified in numerous cell types in the respiratory tract, including sensory neurons, airway epithelial cells, airway smooth muscle cells, and fibroblasts. Different types of TRP channels induce cough in sensory neurons via the vagus nerve. Permeability and cytokine production are also regulated by TRP channels in airway epithelial cells, and these channels also contribute to the modulation of bronchoconstriction. TRP channels may cooperate with other TRP channels, or act in concert with calcium-dependent potassium channels and calcium-activated chloride channel. Hence, TRP channels could be the potential therapeutic targets for chronic airway inflammatory diseases. In this review, we aim to discuss the expression profiles and physiological functions of TRP channels in the airway, and the roles they play in chronic airway inflammatory diseases.

TRPV4: A Physio and Pathophysiologically Significant Ion Channel

“…In this sense, important roles for several TRP channels have been associated to various diseases [16][17][18][19][20]; however, there is still quite a bit of work to be done since the roles of some of these proteins in physiology are still being uncovered. It is important to note that, while some TRP channels have been extensively studied (i.e., TRPV1, the first mammalian TRP channel to be cloned) [7], other members of this family of ion channels have proven to be somewhat more elusive.…”

“…TRP channels are well known to respond to a wide range of molecules that include those that are potentially harmful to an organism [1,99]. In the respiratory airway, TRP channels induce inflammation, airway constriction, mucus secretion, and sneezing and coughing, all of which constitute a mechanism of defense for the respiratory airways [20,98,100].…”

“…The TRPV4 channel is expressed in the smooth muscle, fibroblasts, macrophages, submucosal glands, vascular endothelial cells, and in tracheal, bronchial, and alveolar epithelia [20,22,34,[101][102][103]. Aside from maintaining the homeostasis of osmotic pressure in these tissues, TRPV4 also integrates stimuli of a diverse nature that translate into Ca 2+ signals, promoting different responses in the tissues of the respiratory system [104].…”

Cytochrome P450 Epoxygenase-Dependent Activation of TRPV4 Channel Participates in Enhanced Serotonin-Induced Pulmonary Vasoconstriction in Chronic Hypoxic Pulmonary Hypertension

“…Transient receptor potential (TRP) channels are a set of nonselective cation channels containing seven protein families [8]. TRPV4, serving as an osmo-mechanosensitive channel, is widely expressed and functioning in both systemic and pulmonary vasculatures [9] and is gated by numerous stimuli including moderate heat, shear stress, osmotic, chemical stimuli, and the endogenous agonist, epoxyeicosatrienoic acids (EETs) [8,[10][11][12][13][14][15][16][17][18]. Cytochrome P450 (CYP) epoxygenases, especially CYP 2 group, metabolize membrane arachidonate to generate EETs [19].…”

Estrogen receptors differentially regulate intracellular calcium handling in human nonasthmatic and asthmatic airway smooth muscle cells

“…If ER signaling affects the SR function (as evidenced by the LaCl 3 experiments), it may also modulate regulatory proteins, such as STIM1 and Orai1 that are critical to store-operated calcium entry (SOCE) (17,27,44,74). Furthermore, as transient receptor potential channels and sodium-calcium exchange pumps modulate the SOCE (64,72,82,84), involvement of these mechanisms of long-term ER signaling remain to be examined.…”