MiR-140-3p regulation of TNF-α-induced CD38 expression in human airway smooth muscle cells

Joseph A. Jude, Mythili Dileepan, Subbaya Subramanian, Julian Solway, Reynold A. Panettieri, Reynold A. Panettieri, Timothy F. Walseth, Mathur S. Kannan

Research output: Contribution to journalArticlepeer-review

84 Scopus citations


CD38, a membrane protein expressed in airway smooth muscle (ASM) cells, plays a role in cellular Ca 2+ dynamics and ASM contractility. In human ASM (HASM) cells, TNF-α induces CD38 expression through activation of MAPKs, NF-κB, and AP-1, and its expression is differentially elevated in cells from asthmatic patients compared with cells from nonasthmatic subjects. The CD38 3'-untranslated region (UTR) has targets for miR-140-3p. We hypothesized that miR-140-3p regulates CD38 expression in HASM cells by altering CD38 mRNA stability. Basal and TNF-α-induced expression of miR-140-3p was determined in nonasthmatic ASM (NAASM) and asthmatic ASM (AASM) cells. NAASM and AASM cells were transfected with control, miR-140-3p mimic, or miR-140-3p antagomirs, and CD38 expression and CD38 mRNA stability were determined. Luciferase reporter assays were used to determine miR-140-3p binding to the CD38 3'-UTR. Activation of p38, ERK, and JNK MAPKs, NF-κB, and AP-1 was determined in miR-140-3p mimic-transfected NAASM. TNF-α attenuated miR-140-3p expression in NAASM and AASM cells, but at a greater magnitude in AASM cells. CD38 mRNA expression was attenuated by miR-140-3p mimic at comparable magnitude in NAASM and AASM cells. Mutated miR-140-3p target on the CD38 3'-UTR reversed the inhibition of luciferase activity by miR-140-3p mimic. CD38 mRNA stability was unaltered by miR-140-3p mimic in NAASM or AASM cells following arrest of transcription. TNF-α-induced activation of p38 MAPK and NF-κB was attenuated by miR-140-3p mimic. The findings indicate that miR-140-3p modulates CD38 expression in HASM cells through direct binding to the CD38 3'-UTR and indirect mechanisms involving activation of p38 MAPK and NF-κB. Furthermore, indirect mechanisms appear to play a major role in the regulation of CD38 expression.

Original languageEnglish (US)
Pages (from-to)L460-L468
JournalAmerican Journal of Physiology - Lung Cellular and Molecular Physiology
Issue number5
StatePublished - Sep 1 2012
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Physiology
  • Pulmonary and Respiratory Medicine
  • Physiology (medical)
  • Cell Biology


  • Asthma
  • Gene expression
  • Microrna


Dive into the research topics of 'MiR-140-3p regulation of TNF-α-induced CD38 expression in human airway smooth muscle cells'. Together they form a unique fingerprint.

Cite this