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Target Concepts:
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Query: UMLS:C0020440 (
hypercapnia
)
7,939
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
The elevation of carbon dioxide (CO
2
) in tissues and the bloodstream (
hypercapnia
) occurs in patients with severe lung diseases, including chronic obstructive pulmonary disease (COPD). Whereas
hypercapnia
has been recognized as a marker of COPD severity, a role for
hypercapnia
in disease pathogenesis remains unclear. We provide evidence that CO
2
acts as a signaling molecule in mouse and human airway smooth muscle cells. High CO
2
activated calcium-calpain signaling and consequent smooth muscle cell contraction in mouse airway smooth muscle cells. The signaling was mediated by
caspase-7
-induced down-regulation of the microRNA-133a (miR-133a) and consequent up-regulation of Ras homolog family member A and myosin light-chain phosphorylation. Exposure of wild-type, but not
caspase-7
-null, mice to
hypercapnia
increased airway contraction and resistance. Deletion of the
Caspase-7
gene prevented
hypercapnia
-induced airway contractility, which was restored by lentiviral transfection of a miR-133a antagonist. In a cohort of patients with severe COPD, hypercapnic patients had higher airway resistance, which improved after correction of
hypercapnia
. Our data suggest a specific molecular mechanism by which the development of
hypercapnia
may drive COPD pathogenesis and progression.
...
PMID:Hypercapnia increases airway smooth muscle contractility via caspase-7-mediated miR-133a-RhoA signaling. 3018 50
