NOTCH signaling in lung diseases.

NOTCH is a fundamental signaling system that regulates normal embryonic development and tissue homeostasis in adult life. NOTCH receptor is a single-pass transmembrane protein normally triggered via direct cell-to-cell contact, in which NOTCH ligands bind the extracellular domain of the receptor, inducing γ-secretase cleavage and release of intracellular domain. The intracellular domain binds to the transcriptional effector RBPJκ to activate transcription of target genes that regulate cell differentiation, patterning, and morphogenesis during embryonic development and adult life. Specifically, NOTCH plays an essential role in the development and homeostasis of the lung. Aberrations in NOTCH signaling or components of the signaling system have been linked to various pulmonary pathological conditions. We herein provide a brief overview of collective in vitro and in vivo studies of NOTCH signaling to illustrate its regulatory functions in lung diseases, including asthma, chronic obstructive pulmonary disease, pulmonary arterial hypertension, and lung cancer. We also discuss the mechanisms underlying the regulatory role of NOTCH in these pathological conditions and the potential of NOTCH-targeted therapies for the treatment of these diseases.