CD38/cADPR Signaling Pathway in Airway Disease: Regulatory Mechanisms

Deepak A. Deshpande, Alonso G.P. Guedes, Richard Graeff, Soner Dogan, Subbaya Subramanian, Timothy F. Walseth, Mathur S. Kannan

Research output: Contribution to journalReview articlepeer-review

8 Scopus citations

Abstract

Asthma is an inflammatory disease in which proinflammatory cytokines have a role in inducing abnormalities of airway smooth muscle function and in the development of airway hyperresponsiveness. Inflammatory cytokines alter calcium (Ca2+) signaling and contractility of airway smooth muscle, which results in nonspecific airway hyperresponsiveness to agonists. In this context, Ca2+ regulatory mechanisms in airway smooth muscle and changes in these regulatory mechanisms encompass a major component of airway hyperresponsiveness. Although dynamic Ca2+ regulation is complex, phospholipase C/inositol tris-phosphate (PLC/IP3) and CD38-cyclic ADP-ribose (CD38/cADPR) are two major pathways mediating agonist-induced Ca2+ regulation in airway smooth muscle. Altered CD38 expression or enhanced cyclic ADP-ribosyl cyclase activity associated with CD38 contributes to human pathologies such as asthma, neoplasia, and neuroimmune diseases. This review is focused on investigations on the role of CD38-cyclic ADP-ribose signaling in airway smooth muscle in the context of transcriptional and posttranscriptional regulation of CD38 expression. The specific roles of transcription factors NF-kB and AP-1 in the transcriptional regulation of CD38 expression and of miRNAs miR-140-3p and miR-708 in the posttranscriptional regulation and the underlying mechanisms of such regulation are discussed.

Original languageEnglish (US)
Article number8942042
JournalMediators of inflammation
Volume2018
DOIs
StatePublished - 2018

Bibliographical note

Funding Information:
Mathur S. Kannan and Deepak A. Deshpande received support through grants from the National Institutes of Health.

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