Spns2 Transporter Contributes to the Accumulation of S1P in Cystic Fibrosis Human Bronchial Epithelial Cells
Articolo
Data di Pubblicazione:
2021
Citazione:
Spns2 Transporter Contributes to the Accumulation of S1P in Cystic Fibrosis Human Bronchial Epithelial Cells / A. Zulueta Morales, M.V. Dei Cas, F. Luciano, A. Mingione, F. Pivari, I. Righi, L.C. Morlacchi, L.P.A. Rosso, P. Signorelli, R. Ghidoni, R.C. Paroni, A. Caretti. - In: BIOMEDICINES. - ISSN 2227-9059. - 9:9(2021 Aug 31), pp. 1121.1-1121.14. [10.3390/biomedicines9091121]
Abstract:
The role of S1P in Cystic Fibrosis (CF) has been investigated since 2001, when it was first
described that the CFTR channel regulates the inward transport of S1P. From then on, various
studies have associated F508del CFTR, the most frequent mutation in CF patients, with altered S1P
expression in tissue and plasma. We found that human bronchial epithelial immortalized and
primary cells from CF patients express more S1P than the control cells, as evidenced by mass
spectrometry analysis. S1P accumulation relies on two- to four-fold transcriptional up-regulation of
SphK1 and simultaneous halving of SGPL1 in CF vs. control cells. The reduction of SGPL1
transcription protects S1P from irreversible degradation, but the excessive accumulation is partially
prevented by the action of the two phosphatases that are up-regulated compared to control cells.
For the first time in CF, we describe that Spns2, a non-ATP dependent transporter that normally
extrudes S1P out of the cells, shows deficient transcriptional and protein expression, thus impairing
S1P accrual dissipation. The in vitro data on CF human bronchial epithelia correlates with the
impaired expression of Spns2 observed in CF human lung biopsies compared to healthy control.
Tipologia IRIS:
01 - Articolo su periodico
Keywords:
Spns2; S1P; sphingosine; SphK1; SGPL1; Cystic Fibrosis; sphingolipid; lung;
Elenco autori:
A. ZULUETA MORALES, M.V. DEI CAS, F. Luciano, A. Mingione, F. Pivari, I. Righi, L.C. Morlacchi, L.P.A. Rosso, P. Signorelli, R. Ghidoni, R.C. Paroni, A. Caretti
Link alla scheda completa:
Link al Full Text: