Plumbagin attenuates traumatic tracheal stenosis in rats and inhibits lung fibroblast proliferation and differentiation via TGF-β1/Smad and Akt/mTOR pathways
Traumatic tracheal stenosis (TS) is a serious respiratory disease characterized by hyperplasia of airway granulation. Plumbagin (PLB) is a natural naphthoquinone component with anti-fibrotic properties. This research aimed to explore the roles of PLB in alleviating TS and the underlying mechanisms....
Main Authors: | , , , , , , , , |
---|---|
Format: | Article |
Language: | English |
Published: |
Taylor & Francis Group
2021-01-01
|
Series: | Bioengineered |
Subjects: | |
Online Access: | http://dx.doi.org/10.1080/21655979.2021.1954580 |
id |
doaj-956b6ffc1bd4470bbbcac44aa23a14be |
---|---|
record_format |
Article |
spelling |
doaj-956b6ffc1bd4470bbbcac44aa23a14be2021-07-26T12:59:37ZengTaylor & Francis GroupBioengineered2165-59792165-59872021-01-011214475448810.1080/21655979.2021.19545801954580Plumbagin attenuates traumatic tracheal stenosis in rats and inhibits lung fibroblast proliferation and differentiation via TGF-β1/Smad and Akt/mTOR pathwaysWei Shi0Yuanyuan Fang1Yueming Jiang2Siyang Jiang3Yu Li4Wentao Li5Mingpeng Xu6Michael Aschner7Guangnan Liu8Pulmonary and Critical Care Medicine of The Second Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, ChinaGuangxi Medical UniversityGuangxi Medical UniversityGuangxi Medical UniversityPulmonary and Critical Care Medicine of The Second Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, ChinaGuangxi Medical UniversityPulmonary and Critical Care Medicine of The Second Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, ChinaAlbert Einstein College of MedicinePulmonary and Critical Care Medicine of The Second Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, ChinaTraumatic tracheal stenosis (TS) is a serious respiratory disease characterized by hyperplasia of airway granulation. Plumbagin (PLB) is a natural naphthoquinone component with anti-fibrotic properties. This research aimed to explore the roles of PLB in alleviating TS and the underlying mechanisms. For in vitro studies, lung fibroblasts (IMR-90 cells), with/without PLB treatment or TGF-β1 induction, were used. The viability and proliferation of IMR-90 cells were examined by CCK-8 and EdU incorporation assays. The differentiation of IMR-90 cells was assessed by detecting the mRNA and protein expression levels of collagen (COL)-1 and alpha-smooth muscle actin (α-SMA). Besides, immunofluorescence assay was conducted to evaluate the localization of α-SMA in TGF-β1-induced IMR-90 cells. Moreover, the combination of PLB with/without TβRI (SB-431,542), PI3K/Akt (Ly294002) or mTOR (rapamycin) inhibitor was pretreated on IMR-90 cells after TGF-β1 induction. For in vivo studies, a rat model of TS was established. The pathological features and severity of TS were determined by hematoxylin and eosin staining. The protein levels of TGF-β1/Smad and Akt/mTOR pathways were detected for both in vitro and in vivo models. PLB effectively inhibited the proliferation and differentiation of TGF-β1-induced IMR-90 cells, and suppressed TGF-β1/Smad and Akt/mTOR signaling pathways both in vivo and in vitro. Furthermore, PLB reduced the degree of TS in rats. Taken together, our results indicate that PLB regulates lung fibroblast activity and attenuates TS in rats by inhibiting TGF-β1/Smad and Akt/mTOR signaling pathways. In conclusion, this study implies that PLB may serve as a promising therapeutic compound for TS.http://dx.doi.org/10.1080/21655979.2021.1954580tracheal stenosisplumbagintgf-β1aktsamd2/3mtorfibroblastproliferationdifferentiation |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Wei Shi Yuanyuan Fang Yueming Jiang Siyang Jiang Yu Li Wentao Li Mingpeng Xu Michael Aschner Guangnan Liu |
spellingShingle |
Wei Shi Yuanyuan Fang Yueming Jiang Siyang Jiang Yu Li Wentao Li Mingpeng Xu Michael Aschner Guangnan Liu Plumbagin attenuates traumatic tracheal stenosis in rats and inhibits lung fibroblast proliferation and differentiation via TGF-β1/Smad and Akt/mTOR pathways Bioengineered tracheal stenosis plumbagin tgf-β1 akt samd2/3 mtor fibroblast proliferation differentiation |
author_facet |
Wei Shi Yuanyuan Fang Yueming Jiang Siyang Jiang Yu Li Wentao Li Mingpeng Xu Michael Aschner Guangnan Liu |
author_sort |
Wei Shi |
title |
Plumbagin attenuates traumatic tracheal stenosis in rats and inhibits lung fibroblast proliferation and differentiation via TGF-β1/Smad and Akt/mTOR pathways |
title_short |
Plumbagin attenuates traumatic tracheal stenosis in rats and inhibits lung fibroblast proliferation and differentiation via TGF-β1/Smad and Akt/mTOR pathways |
title_full |
Plumbagin attenuates traumatic tracheal stenosis in rats and inhibits lung fibroblast proliferation and differentiation via TGF-β1/Smad and Akt/mTOR pathways |
title_fullStr |
Plumbagin attenuates traumatic tracheal stenosis in rats and inhibits lung fibroblast proliferation and differentiation via TGF-β1/Smad and Akt/mTOR pathways |
title_full_unstemmed |
Plumbagin attenuates traumatic tracheal stenosis in rats and inhibits lung fibroblast proliferation and differentiation via TGF-β1/Smad and Akt/mTOR pathways |
title_sort |
plumbagin attenuates traumatic tracheal stenosis in rats and inhibits lung fibroblast proliferation and differentiation via tgf-β1/smad and akt/mtor pathways |
publisher |
Taylor & Francis Group |
series |
Bioengineered |
issn |
2165-5979 2165-5987 |
publishDate |
2021-01-01 |
description |
Traumatic tracheal stenosis (TS) is a serious respiratory disease characterized by hyperplasia of airway granulation. Plumbagin (PLB) is a natural naphthoquinone component with anti-fibrotic properties. This research aimed to explore the roles of PLB in alleviating TS and the underlying mechanisms. For in vitro studies, lung fibroblasts (IMR-90 cells), with/without PLB treatment or TGF-β1 induction, were used. The viability and proliferation of IMR-90 cells were examined by CCK-8 and EdU incorporation assays. The differentiation of IMR-90 cells was assessed by detecting the mRNA and protein expression levels of collagen (COL)-1 and alpha-smooth muscle actin (α-SMA). Besides, immunofluorescence assay was conducted to evaluate the localization of α-SMA in TGF-β1-induced IMR-90 cells. Moreover, the combination of PLB with/without TβRI (SB-431,542), PI3K/Akt (Ly294002) or mTOR (rapamycin) inhibitor was pretreated on IMR-90 cells after TGF-β1 induction. For in vivo studies, a rat model of TS was established. The pathological features and severity of TS were determined by hematoxylin and eosin staining. The protein levels of TGF-β1/Smad and Akt/mTOR pathways were detected for both in vitro and in vivo models. PLB effectively inhibited the proliferation and differentiation of TGF-β1-induced IMR-90 cells, and suppressed TGF-β1/Smad and Akt/mTOR signaling pathways both in vivo and in vitro. Furthermore, PLB reduced the degree of TS in rats. Taken together, our results indicate that PLB regulates lung fibroblast activity and attenuates TS in rats by inhibiting TGF-β1/Smad and Akt/mTOR signaling pathways. In conclusion, this study implies that PLB may serve as a promising therapeutic compound for TS. |
topic |
tracheal stenosis plumbagin tgf-β1 akt samd2/3 mtor fibroblast proliferation differentiation |
url |
http://dx.doi.org/10.1080/21655979.2021.1954580 |
work_keys_str_mv |
AT weishi plumbaginattenuatestraumatictrachealstenosisinratsandinhibitslungfibroblastproliferationanddifferentiationviatgfb1smadandaktmtorpathways AT yuanyuanfang plumbaginattenuatestraumatictrachealstenosisinratsandinhibitslungfibroblastproliferationanddifferentiationviatgfb1smadandaktmtorpathways AT yuemingjiang plumbaginattenuatestraumatictrachealstenosisinratsandinhibitslungfibroblastproliferationanddifferentiationviatgfb1smadandaktmtorpathways AT siyangjiang plumbaginattenuatestraumatictrachealstenosisinratsandinhibitslungfibroblastproliferationanddifferentiationviatgfb1smadandaktmtorpathways AT yuli plumbaginattenuatestraumatictrachealstenosisinratsandinhibitslungfibroblastproliferationanddifferentiationviatgfb1smadandaktmtorpathways AT wentaoli plumbaginattenuatestraumatictrachealstenosisinratsandinhibitslungfibroblastproliferationanddifferentiationviatgfb1smadandaktmtorpathways AT mingpengxu plumbaginattenuatestraumatictrachealstenosisinratsandinhibitslungfibroblastproliferationanddifferentiationviatgfb1smadandaktmtorpathways AT michaelaschner plumbaginattenuatestraumatictrachealstenosisinratsandinhibitslungfibroblastproliferationanddifferentiationviatgfb1smadandaktmtorpathways AT guangnanliu plumbaginattenuatestraumatictrachealstenosisinratsandinhibitslungfibroblastproliferationanddifferentiationviatgfb1smadandaktmtorpathways |
_version_ |
1721281215182405632 |