The Pivotal Role of Airway Smooth Muscle in Asthma Pathophysiology

Figure 1

Impaired ASM cell calcium homeostasis leading to enhanced proliferation in asthma. In severe asthmatic ASM cells, an altered calcium homeostasis related to an increased influx leads to phosphorylation and activation of CaMK-IV, that, in turns, successively activates PGC-1α, NRF-1, and mtTFA. This transduction pathway results in an increase of mitochondrial biogenesis leading to enhanced ASM proliferation [61]. In nonsevere asthmatic ASM cells, an altered expression and function of SERCA2 may account for the altered calcium homeostasis, which leads to enhanced ASM proliferation [62]. Whatever the mechanism, such altered calcium homeostasis enhances cell contractility. ASM: airway smooth muscle; CaMK-IV: calcium/calmodulin-dependent protein kinase IV; G: G protein; mtTFA: mitochondrial transcription factor A; NRF: nuclear respiratory factor; PGC: peroxisome proliferator-activated receptor γ coactivator; PLC: phospholipase C; SERCA: sarcoendoplasmic calcium pomp; SR: sarcoplasmic reticulum.