Tirbanibulin Attenuates Pulmonary Fibrosis by Modulating Src/STAT3 Signaling
Tirbanibulin (KX-01) is the first clinical Src inhibitor of the novel peptidomimetic class that targets the peptide substrate site of Src providing more specificity toward the Src kinase. This study assessed the impact of KX-01 on cobalt chloride (CoCl2)-treated L929 cells and bleomycin (BLM)-induce...
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doaj-d85ce68a191b4bf0b46e99b542c092562021-07-19T06:39:39ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122021-07-011210.3389/fphar.2021.693906693906Tirbanibulin Attenuates Pulmonary Fibrosis by Modulating Src/STAT3 SignalingXin Wang0Rui Ren1Zehui Xu2Haidi Huang3Wanglin Jiang4Jinbo Ma5School of Pharmacy, Binzhou Medical University, Yantai, ChinaSchool of Pharmacy, Binzhou Medical University, Yantai, ChinaSchool of Pharmacy, Binzhou Medical University, Yantai, ChinaSchool of Pharmacy, Binzhou Medical University, Yantai, ChinaSchool of Pharmacy, Binzhou Medical University, Yantai, ChinaMedicine & Pharmacy Research Center, Binzhou Medical University, Yantai, ChinaTirbanibulin (KX-01) is the first clinical Src inhibitor of the novel peptidomimetic class that targets the peptide substrate site of Src providing more specificity toward the Src kinase. This study assessed the impact of KX-01 on cobalt chloride (CoCl2)-treated L929 cells and bleomycin (BLM)-induced pulmonary fibrosis in rats to evaluate the efficacy of this compound in vitro and in vivo, respectively. In CoCl2-treated L929 cells, KX-01 significantly reduced the expression of smooth muscle actin (α-SMA), collagen I, collagen III, hypoxia inducing factor (HIF-1α), signal transducers and transcriptional activators (p-STAT3), and p-Src. In BLM-induced pulmonary fibrosis rats, KX-01 reduced pathological scores, collagen deposition, α-SMA, collagen I, collagen III, p-Src, HIF-1α, and p-STAT3. Overall, these findings revealed that KX-01 can alleviate experimental pulmonary fibrosis via suppressing the p-SRC/p-STAT3 signaling pathways.https://www.frontiersin.org/articles/10.3389/fphar.2021.693906/fullpulmonary fibrosistirbanibulinp-SrcHIF-1αP-STAT3 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Xin Wang Rui Ren Zehui Xu Haidi Huang Wanglin Jiang Jinbo Ma |
spellingShingle |
Xin Wang Rui Ren Zehui Xu Haidi Huang Wanglin Jiang Jinbo Ma Tirbanibulin Attenuates Pulmonary Fibrosis by Modulating Src/STAT3 Signaling Frontiers in Pharmacology pulmonary fibrosis tirbanibulin p-Src HIF-1α P-STAT3 |
author_facet |
Xin Wang Rui Ren Zehui Xu Haidi Huang Wanglin Jiang Jinbo Ma |
author_sort |
Xin Wang |
title |
Tirbanibulin Attenuates Pulmonary Fibrosis by Modulating Src/STAT3 Signaling |
title_short |
Tirbanibulin Attenuates Pulmonary Fibrosis by Modulating Src/STAT3 Signaling |
title_full |
Tirbanibulin Attenuates Pulmonary Fibrosis by Modulating Src/STAT3 Signaling |
title_fullStr |
Tirbanibulin Attenuates Pulmonary Fibrosis by Modulating Src/STAT3 Signaling |
title_full_unstemmed |
Tirbanibulin Attenuates Pulmonary Fibrosis by Modulating Src/STAT3 Signaling |
title_sort |
tirbanibulin attenuates pulmonary fibrosis by modulating src/stat3 signaling |
publisher |
Frontiers Media S.A. |
series |
Frontiers in Pharmacology |
issn |
1663-9812 |
publishDate |
2021-07-01 |
description |
Tirbanibulin (KX-01) is the first clinical Src inhibitor of the novel peptidomimetic class that targets the peptide substrate site of Src providing more specificity toward the Src kinase. This study assessed the impact of KX-01 on cobalt chloride (CoCl2)-treated L929 cells and bleomycin (BLM)-induced pulmonary fibrosis in rats to evaluate the efficacy of this compound in vitro and in vivo, respectively. In CoCl2-treated L929 cells, KX-01 significantly reduced the expression of smooth muscle actin (α-SMA), collagen I, collagen III, hypoxia inducing factor (HIF-1α), signal transducers and transcriptional activators (p-STAT3), and p-Src. In BLM-induced pulmonary fibrosis rats, KX-01 reduced pathological scores, collagen deposition, α-SMA, collagen I, collagen III, p-Src, HIF-1α, and p-STAT3. Overall, these findings revealed that KX-01 can alleviate experimental pulmonary fibrosis via suppressing the p-SRC/p-STAT3 signaling pathways. |
topic |
pulmonary fibrosis tirbanibulin p-Src HIF-1α P-STAT3 |
url |
https://www.frontiersin.org/articles/10.3389/fphar.2021.693906/full |
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