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Post‐Transcriptional Regulation of CD38 expression in human airway smooth muscle (HASM) cells
Author(s) -
Jude Joseph Antony,
Puvanendiran Shanmugam,
Walseth Timothy,
Solway Julian,
Panettieri Reynold,
Kannan Mathur S
Publication year - 2010
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.24.1_supplement.626.6
Subject(s) - cd38 , messenger rna , microrna , transfection , microbiology and biotechnology , transcriptional regulation , chemistry , cell culture , biology , gene expression , gene , stem cell , biochemistry , genetics , cd34
CD38 is a membrane protein expressed in HASM cells and its induction by TNF‐α involves transcriptional and post‐transcriptional mechanisms. CD38‐null mice develop attenuated airway hyperresponsiveness compared to the wild‐type mice. TNF‐α causes greater elevation of CD38 expression in asthmatic HASM cells than in non‐asthmatic cells. The objectives of this study were to determine the role of 1) RNA binding protein HuR and 2) microRNAs in post‐transcriptional regulation of CD38 expression in HASM cells. Expression and sub‐cellular localization of HuR were determined by western blotting. CD38 mRNA stability was determined in HASM cells transiently transfected with HuR. Binding of HuR to an oligonucleotide representing the AU‐rich motif (ARE) of CD38 mRNA was determined by a pull‐down assay. Expression of the miRNA miR‐140‐3p was determined by qRT‐PCR. In HASM cells, HuR was localized to the nuclei and its expression was unaltered by TNF‐α, although TNF‐α exposure increased HuR binding to the oligo mimicking ARE of the CD38 3′UTR. CD38 mRNA decay and HuR levels were comparable in non‐asthmatic and asthmatic cells. HuR overexpression did not alter CD38 mRNA decay. MiR‐140‐3p expression was unaltered in non‐asthmatic cells by TNF‐α, whereas in asthmatic cells it was reduced. The differential induction of CD38 expression by TNF‐α in asthmatic ASM cells may arise from regulation by miR‐140‐3p, but not HuR, expression.