Therapeutic potential of amitriptyline for paraquat-induced pulmonary
fibrosis: involvement of caveolin-1-mediated anti-epithelial-mesenchymal
transition and inhibition of apoptosis
Abstract
The present study was performed to investigate the anti-fibrotic effect
of Amitriptyline (AMT) on paraquat (PQ)-induced pulmonary fibrosis and
its possible mechanism. A total of 32 C57BL/6 mice were randomly divided
into control, PQ, PQ + AMT and AMT groups. Lung histopathology, blood
gas analysis, hydroxyproline (HYP), TGF-β1 and IL-17 were measured.
E-cadherin, N-cadherin, α-SMA and caveolin-1 were studied by
immunohistochemistry and Western-blot analysis in mice and A549 cells.
As we found that, compared with the PQ group, the PQ + AMT group
displayed mild pathological changes in pulmonary fibrosis, lower HYP,
IL-17 and TGF- β1 levels in lung, and levels of N-cadherin and α-SMA in
the lungs were significantly decreased, but caveolin-1 was increased (p
< 0.01). While SaO2 and PaO2 levels were higher. Compared with
the PQ group, the apoptosis rate, N-cadherin and α-SMA levels in the
A549 cells were significantly decreased after PQ treatment and high-dose
AMT intervention (p < 0.01). The expressions of E-cadherin,
N-cadherin and -SMA in the PQ-induced cells transfected with caveolin-1
siRNA or siControl RNA were significantly different (p <
0.01). Our results suggested that AMT inhibits PQ-induced EMT in A549
cells and improves lung histopathology and oxygenation in mice by
up-regulating caveolin-1.