Figure 8. RA signaling in ASM maintains normal ASM phenotype by preventing excessive activation of the TGF-β pathway.

Left: Tonic RA signaling in ASM keeps TGF-β activity in ASM at a low level to maintain normal ASM phenotype. Right: Disruption of RA signaling in ASM leads to increased TGF-β ligand production and TGF-β pathway activation, causing increased ECM deposition, ASM hypertrophy, ASM hypercontractility, and airway remodeling, ultimately resulting in higher airway resistance and AHR. Autoinduction of TGF-β ligand and inhibition of RA receptor–mediated signaling by TGF-β results in persistent TGF-β activation.