Derrone Targeting the TGF Type 1 Receptor Kinase Improves Bleomycin-Mediated Pulmonary Fibrosis through Inhibition of Smad Signaling Pathway Article Swipe
Ilandarage Menu Neelaka Molagoda
,
Sobarathne Senel Sanjaya
,
Kyoung Tae Lee
,
Yung Hyun Choi
,
Joyce H. Lee
,
Mi‐Hwa Lee
,
Chang‐Hee Kang
,
Chang-Min Lee
,
Gi‐Young Kim
·
YOU?
·
· 2023
· Open Access
·
· DOI: https://doi.org/10.3390/ijms24087265
YOU?
·
· 2023
· Open Access
·
· DOI: https://doi.org/10.3390/ijms24087265
Transforming growth factor-β (TGF-β) has a strong impact on the pathogenesis of pulmonary fibrosis. Therefore, in this study, we investigated whether derrone promotes anti-fibrotic effects on TGF-β1-stimulated MRC-5 lung fibroblast cells and bleomycin-induced lung fibrosis. Long-term treatment with high concentrations of derrone increased the cytotoxicity of MRC-5 cells; however, substantial cell death was not observed at low concentrations of derrone (below 0.05 μg/mL) during a three-day treatment. In addition, derrone significantly decreased the expressions of TGF-β1, fibronectin, elastin, and collagen1α1, and these decreases were accompanied by downregulation of α-SMA expression in TGF-β1-stimulated MRC-5 cells. Severe fibrotic histopathological changes in infiltration, alveolar congestion, and alveolar wall thickness were observed in bleomycin-treated mice; however, derrone supplementation significantly reduced these histological deformations. In addition, intratracheal administration of bleomycin resulted in lung collagen accumulation and high expression of α-SMA and fibrotic genes—including TGF-β1, fibronectin, elastin, and collagen1α1—in the lungs. However, fibrotic severity in intranasal derrone-administrated mice was significantly less than that of bleomycin-administered mice. Molecular docking predicted that derrone potently fits into the ATP-binding pocket of the TGF-β receptor type 1 kinase domain with stronger binding scores than ATP. Additionally, derrone inhibited TGF-β1-induced phosphorylation and nuclear translocations of Smad2/3. Overall, derrone significantly attenuated TGF-β1-stimulated lung inflammation in vitro and bleomycin-induced lung fibrosis in a murine model, indicating that derrone may be a promising candidate for preventing pulmonary fibrosis.
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- Type
- article
- Language
- en
- Landing Page
- https://doi.org/10.3390/ijms24087265
- https://www.mdpi.com/1422-0067/24/8/7265/pdf?version=1681459409
- OA Status
- gold
- Cited By
- 6
- References
- 47
- Related Works
- 10
- OpenAlex ID
- https://openalex.org/W4365513624
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- OpenAlex ID
-
https://openalex.org/W4365513624Canonical identifier for this work in OpenAlex
- DOI
-
https://doi.org/10.3390/ijms24087265Digital Object Identifier
- Title
-
Derrone Targeting the TGF Type 1 Receptor Kinase Improves Bleomycin-Mediated Pulmonary Fibrosis through Inhibition of Smad Signaling PathwayWork title
- Type
-
articleOpenAlex work type
- Language
-
enPrimary language
- Publication year
-
2023Year of publication
- Publication date
-
2023-04-14Full publication date if available
- Authors
-
Ilandarage Menu Neelaka Molagoda, Sobarathne Senel Sanjaya, Kyoung Tae Lee, Yung Hyun Choi, Joyce H. Lee, Mi‐Hwa Lee, Chang‐Hee Kang, Chang-Min Lee, Gi‐Young KimList of authors in order
- Landing page
-
https://doi.org/10.3390/ijms24087265Publisher landing page
- PDF URL
-
https://www.mdpi.com/1422-0067/24/8/7265/pdf?version=1681459409Direct link to full text PDF
- Open access
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YesWhether a free full text is available
- OA status
-
goldOpen access status per OpenAlex
- OA URL
-
https://www.mdpi.com/1422-0067/24/8/7265/pdf?version=1681459409Direct OA link when available
- Concepts
-
SMAD, Bleomycin, Signal transduction, Smad2 Protein, Pulmonary fibrosis, Transforming growth factor, Cancer research, Receptor, Cell biology, Medicine, Chemistry, Pharmacology, Fibrosis, Biology, Internal medicine, ChemotherapyTop concepts (fields/topics) attached by OpenAlex
- Cited by
-
6Total citation count in OpenAlex
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2025: 3, 2024: 2, 2023: 1Per-year citation counts (last 5 years)
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47Number of works referenced by this work
- Related works (count)
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10Other works algorithmically related by OpenAlex
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| abstract_inverted_index.fibrosis. | 13, 34, 223 |
| abstract_inverted_index.increased | 42 |
| abstract_inverted_index.inhibited | 187 |
| abstract_inverted_index.predicted | 162 |
| abstract_inverted_index.promising | 218 |
| abstract_inverted_index.pulmonary | 12, 222 |
| abstract_inverted_index.thickness | 105 |
| abstract_inverted_index.three-day | 65 |
| abstract_inverted_index.treatment | 36 |
| abstract_inverted_index.Therefore, | 14 |
| abstract_inverted_index.attenuated | 198 |
| abstract_inverted_index.expression | 89, 132 |
| abstract_inverted_index.fibroblast | 29 |
| abstract_inverted_index.indicating | 212 |
| abstract_inverted_index.intranasal | 149 |
| abstract_inverted_index.preventing | 221 |
| abstract_inverted_index.treatment. | 66 |
| abstract_inverted_index.ATP-binding | 169 |
| abstract_inverted_index.accompanied | 84 |
| abstract_inverted_index.congestion, | 101 |
| abstract_inverted_index.expressions | 73 |
| abstract_inverted_index.substantial | 49 |
| abstract_inverted_index.Transforming | 0 |
| abstract_inverted_index.accumulation | 129 |
| abstract_inverted_index.cytotoxicity | 44 |
| abstract_inverted_index.fibronectin, | 76, 139 |
| abstract_inverted_index.histological | 117 |
| abstract_inverted_index.inflammation | 201 |
| abstract_inverted_index.investigated | 19 |
| abstract_inverted_index.pathogenesis | 10 |
| abstract_inverted_index.Additionally, | 185 |
| abstract_inverted_index.anti-fibrotic | 23 |
| abstract_inverted_index.collagen1α1, | 79 |
| abstract_inverted_index.deformations. | 118 |
| abstract_inverted_index.infiltration, | 99 |
| abstract_inverted_index.intratracheal | 121 |
| abstract_inverted_index.significantly | 70, 114, 153, 197 |
| abstract_inverted_index.administration | 122 |
| abstract_inverted_index.concentrations | 39, 57 |
| abstract_inverted_index.downregulation | 86 |
| abstract_inverted_index.translocations | 192 |
| abstract_inverted_index.TGF-β1-induced | 188 |
| abstract_inverted_index.phosphorylation | 189 |
| abstract_inverted_index.supplementation | 113 |
| abstract_inverted_index.bleomycin-induced | 32, 205 |
| abstract_inverted_index.bleomycin-treated | 109 |
| abstract_inverted_index.collagen1α1—in | 142 |
| abstract_inverted_index.genes—including | 137 |
| abstract_inverted_index.histopathological | 96 |
| abstract_inverted_index.TGF-β1-stimulated | 26, 91, 199 |
| abstract_inverted_index.derrone-administrated | 150 |
| abstract_inverted_index.bleomycin-administered | 158 |
| cited_by_percentile_year.max | 97 |
| cited_by_percentile_year.min | 89 |
| corresponding_author_ids | https://openalex.org/A5049276892, https://openalex.org/A5102005826 |
| countries_distinct_count | 3 |
| institutions_distinct_count | 9 |
| corresponding_institution_ids | https://openalex.org/I27804330 |
| sustainable_development_goals[0].id | https://metadata.un.org/sdg/3 |
| sustainable_development_goals[0].score | 0.7400000095367432 |
| sustainable_development_goals[0].display_name | Good health and well-being |
| citation_normalized_percentile.value | 0.85547516 |
| citation_normalized_percentile.is_in_top_1_percent | False |
| citation_normalized_percentile.is_in_top_10_percent | False |