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Vistusertib improves pulmonary inflammation and fibrosis by modulating inflammatory/oxidative stress mediators via suppressing the mTOR signalling

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Inflammation Research Aims and scope Submit manuscript



Inflammation and oxidative stress are key factors in the development of pulmonary fibrosis (PF) by promoting the differentiation of fibroblasts through modulating various pathways including Wnt/β-catenin, TGF-β and mTOR signalling.

Objective and methods

This study aimed to evaluate the effects and elucidate the mechanisms of vistusertib (VSB) in treating pulmonary inflammation/fibrosis, specifically by targeting the mTOR pathway using various in vitro and in vivo models.


Lipopolysaccharide (LPS)-induced inflammation model in macrophages (RAW 264.7), epithelial (BEAS-2B) and endothelial (HMVEC-L) cells revealed that treatment with VSB significantly reduced the IL-6, TNF-α, CCL2, and CCL7 expression. TGF-β induced differentiation was also significantly reduced upon VSB treatment in fibrotic cells (LL29 and DHLF). Further, bleomycin-induced inflammation and fibrosis models demonstrated that treatment with VSB significantly ameliorated the severe inflammation, and lung architectural distortion, by reducing the inflammatory markers expression/levels, inflammatory cells and oxidative stress indicators. Further, fibrosis model results exhibited that, VSB treatment significantly reduced the α-SMA, collagen and TGF-β expressions, improved the lung architecture and restored lung functions.


Overall, this study uncovers the anti-inflammatory/anti-fibrotic effects of VSB by modulating the mTOR activation. Although VSB was tested for lung fibrosis, it can be tested for other fibrotic disorders to improve the patient’s survival and quality of life.

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Data availability

No datasets were generated or analysed during the current study.



α-Smooth muscle actin


Alveolar epithelial cells




Chemokine (CC-motif) ligand


Cluster of differentiation








Extracellular matrix


Epithelial-mesenchymal transition


Fetal bovine serum


Fibronectin 1


Heme oxygenase-1






Interstitial lung diseases


Idiopathic pulmonary fibrosis




Monocyte chemoattractant protein-1


Matrix metalloproteinase




Mammalian target of Rapamycin


Neutrophil elastase


Nitric oxide


Phosphate buffer saline


Phosphoinositide 3-kinase


PirfenidoneROS: Reactive oxygen species


Tumor growth factor-β


Tumor necrosis factor




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Authors thank the Director, CSIR-IICT, Hyderabad, India, for providing the facilities and funding necessary for the conducting of this work. T.B.S acknowledges the Council of Scientific and Industrial Research, New Delhi for providing SRF. Authors acknowledges Dr Ramesh Ummanni for help on mTOR antibodies.


Used internal funds of the institute. This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

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Conceptualization: S.R.K, S.B.A; Methodology: T. B.S, S.B.A; In vitro cell culture: T.B.S.; RT-qPCR, Western-blot analysis: T.B.S; In vivo experiments: T.B.S, S.B.A, and C.Yogesh; Manuscript writing - review & editing: T.B.S, S.B.A, and S. R. K.; funding acquisition: S.R.K and S.B.A.

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Correspondence to Sai Balaji Andugulapati or Ramakrishna Sistla.

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Shaikh, T.B., Chandra, Y., Andugulapati, S.B. et al. Vistusertib improves pulmonary inflammation and fibrosis by modulating inflammatory/oxidative stress mediators via suppressing the mTOR signalling. Inflamm. Res. 73, 1223–1237 (2024).

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