JOURNAL ARTICLE
RESEARCH SUPPORT, NON-U.S. GOV'T
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Role of adenylate kinase type 7 expression on cilia motility: possible link in primary ciliary dyskinesia.

BACKGROUND: Adenylate kinase 7 (AK7) mediates the reaction 2ADP <--> ATP + AMP, providing energy for the beating of cilia. A study recently showed that AK7 expression may be correlated with the primary ciliary dyskinesia (PCD) phenotype in mice. In this study, we characterized AK7 expression in vitro in an air-liquid interface (ALI) model and in middle nasal turbinate biopsy specimens from a cohort of patients with PCD to elucidate whether AK7 expression is correlated with ciliary malfunction.

METHODS: AK7 expression was measured by real-time reverse-transcription polymerase chain reaction and Western blotting. In vitro differentiated nasal human epithelial cell siRNA experiments were performed to investigate the effect of AK7 expression on ciliary beat frequency (CBF). Ciliary motility and ultrastructure were evaluated in a cohort of 29 patients with PCD (PCD, n = 17; Kartagener's syndrome, n = 12) and 26 healthy control donors.

RESULTS: AK7 expression was mainly located on the apical surface of differentiated nasal ALI cells, and targeted suppression of the AK7 gene decreased CBF by 41%. AK7 expression was diminished significantly in patients with PCD (0.54 +/- 0.1-fold; p < 0.05) compared with healthy controls (1.1 +/- 0.08-fold). Furthermore, AK7 expression was correlated with CBF in patients with PCD (r = 0.5; p = 0.009).

CONCLUSION: AK7 expression was correlated with CBF in vitro and in nasal biopsy specimens from patients with PCD, which may have contributed to the ciliary malfunction observed in our patients with PCD.

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