Nintedanib exerts anti-pulmonary fibrosis activity via inhibiting TANK-binding kinase 1 (TBK1) phosphorylation

2022 ◽  
Author(s):  
Manru Li ◽  
Yu Zhou ◽  
Tiantian Wang ◽  
Menglin Li ◽  
Xiong Chen ◽  
...  
Keyword(s):  
Pulmonary Fibrosis ◽  
Multikinase Inhibitor ◽  
Functional Mechanism

We described a chemoproteomics approach to identify TBK1 as a key target of the multikinase inhibitor nintedanib in IPF. This insight may facilitate a better understanding of the functional mechanism of nintedanib for antifibrosis efficacy.

Quantitative Microscopic Comparison of the Organization of the Lung in Transgenic Mice Expressing Transforming Growth Factor-α (TGF-α)

1996 ◽  
Vol 54 ◽  
pp. 14-15
Author(s):  
C. G. Plopper ◽  
C. Helton ◽  
A. J. Weir ◽  
J. A. Whitsett ◽  
T. R. Korfhagen
Keyword(s):  
Growth Factor ◽  
Pulmonary Fibrosis ◽  
Transgenic Mice ◽  
Blood Vessels ◽  
Lung Parenchyma ◽  
Lung Maturation ◽  
Alveolar Air ◽  
Parenchymal Tissue ◽  
Air Space ◽  
Conducting Airways

A wide variety of growth factors are thought to be involved in the regulation of pre- and postnatal lung maturation, including factors which bind to the epidermal growth factor receptor. Marked pulmonary fibrosis and enlarged alveolar air spaces have been observed in lungs of transgenic mice expressing human TGF-α under control of the 3.7 KB human SP-C promoter. To test whether TGF-α alters lung morphogenesis and cellular differentiation, we examined morphometrically the lungs of adult (6-10 months) mice derived from line 28, which expresses the highest level of human TGF-α transcripts among transgenic lines. Total volume of lungs (LV) fixed by airway infusion at standard pressure was similar in transgenics and aged-matched non-transgenic mice (Fig. 1). Intrapulmonary bronchi and bronchioles made up a smaller percentage of LV in transgenics than in non-transgenics (Fig. 2). Pulmonary arteries and pulmonary veins were a smaller percentage of LV in transgenic mice than in non-transgenics (Fig. 3). Lung parenchyma (lung tissue free of large vessels and conducting airways) occupied a larger percentage of LV in transgenics than in non-transgenics (Fig. 4). The number of generations of branching in conducting airways was significantly reduced in transgenics as compared to non-transgenic mice. Alveolar air space size, as measured by mean linear intercept, was almost twice as large in transgenic mice as in non-transgenics, especially when different zones within the lung were compared (Fig. 5). Alveolar air space occupied a larger percentage of the lung parenchyma in transgenic mice than in non-transgenic mice (Fig. 6). Collagen abundance was estimated in histological sections as picro-Sirius red positive material by previously-published methods. In intrapulmonary conducting airways, collagen was 4.8% of the wall in transgenics and 4.5% of the wall in non-transgenic mice. Since airways represented a smaller percentage of the lung in transgenics, the volume of interstitial collagen associated with airway wall was significantly less. In intrapulmonary blood vessels, collagen was 8.9% of the wall in transgenics and 0.7% of the wall in non-transgenics. Since blood vessels were a smaller percentage of the lungs in transgenics, the volume of collagen associated with the walls of blood vessels was five times greater. In the lung parenchyma, collagen was 51.5% of the tissue volume in transgenics and 21.2% in non-transgenics. Since parenchyma was a larger percentage of lung volume in transgenics, but the parenchymal tissue was a smaller percent of the volume, the volume of collagen associated with parenchymal tissue was only slightly greater. We conclude that overexpression of TGF-α during lung maturation alters many aspects of lung development, including branching morphogenesis of the airways and vessels and alveolarization in the parenchyma. Further, the increases in visible collagen previously associated with pulmonary fibrosis due to the overexpression of TGF-α are a result of actual increases in amounts of collagen and in a redistribution of collagen within compartments which results from morphogenetic changes. These morphogenetic changes vary by lung compartment. Supported by HL20748, ES06700 and the Cystic Fibrosis Foundation.

microRNA regulation of WISP1 in pulmonary fibrosis: an in silico approach

Pneumologie ◽  
2011 ◽  
Vol 65 (12) ◽  
Author(s):  
B Berschneider ◽  
D Ellwanger ◽  
C Thiel ◽  
V Stümpflen ◽  
M Königshoff
Keyword(s):  
Pulmonary Fibrosis ◽  
In Silico ◽  
Microrna Regulation

Role of Wnt/PCP pathway on bronchial cell function in Idiopathic Pulmonary Fibrosis

Pneumologie ◽  
2011 ◽  
Vol 65 (12) ◽  
Author(s):  
S Barkha ◽  
M Gegg ◽  
H Lickert ◽  
M Königshoff
Keyword(s):  
Idiopathic Pulmonary Fibrosis ◽  
Pulmonary Fibrosis ◽  
Cell Function

The role of Forkhead Box O 3a (FoxO3a) Transcription Factors in the Pathogenesis of Pulmonary Fibrosis

Pneumologie ◽  
2012 ◽  
Vol 66 (06) ◽  
Author(s):  
HM Al-Tamari ◽  
M Eschenhagen ◽  
A Schmall ◽  
R Savai ◽  
HA Ghofrani ◽  
...  
Keyword(s):  
Transcription Factors ◽  
Pulmonary Fibrosis ◽  
Forkhead Box

Regulation of Macroautophagy in Idiopathic Pulmonary Fibrosis

Pneumologie ◽  
2012 ◽  
Vol 66 (06) ◽  
Author(s):  
P Mahavadi ◽  
S Ahuja ◽  
I Henneke ◽  
W Klepetko ◽  
C Ruppert ◽  
...  
Keyword(s):  
Idiopathic Pulmonary Fibrosis ◽  
Pulmonary Fibrosis

Remodelling-related molecular profiles in interstitial pulmonary fibrosis

Pneumologie ◽  
2012 ◽  
Vol 66 (06) ◽  
Author(s):  
D Jonigk ◽  
J Rische ◽  
L Maegel ◽  
H Golpon ◽  
N Izykowski ◽  
...  
Keyword(s):  
Pulmonary Fibrosis ◽  
Interstitial Pulmonary Fibrosis ◽  
Molecular Profiles

Role of JAK-STAT pathway in pulmonary fibrosis

Pneumologie ◽  
2013 ◽  
Vol 67 (05) ◽  
Author(s):  
J Eschenbrenner ◽  
W Janssen ◽  
B Kojonazarov ◽  
K Murmann ◽  
A Ghofrani ◽  
...  
Keyword(s):  
Pulmonary Fibrosis ◽  
Stat Pathway
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