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The target of celastrol acting on HSP60 against pulmonary fibrosis
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Yu ZHOU1, Ya-zi WEI1, Tian-ming YANG2, *, Tian-tai ZHANG1, *
Acta Pharmaceutica Sinica | 2023, 58(3) : 688 - 694
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Acta Pharmaceutica Sinica | 2023, 58(3): 688-694
• Original Articles •
The target of celastrol acting on HSP60 against pulmonary fibrosis
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Yu ZHOU1, Ya-zi WEI1, Tian-ming YANG2, *, Tian-tai ZHANG1, *
Affiliations
  • 1. State Key Laboratory of Bioactive Substance and Function of Nature Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China
  • 2. Tianjin Key Laboratory of Molecular Design and Drug Discovery, Tianjin Institute of Pharmaceutical Research, Tianjin 300301, China
Published: 2023-03-12 doi: 10.16438/j.0513-4870.2022-0983
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Celastrol, extracted from Tripterygium wilfordii, is a natural pentacyclic triterpene compound, which has an anti-pulmonary fibrosis effect. However, its effect, binding targets and regulatory mechanism in pulmonary fibroblasts remain unclear. In this study, we found that celastrol could prevent fibroblast-myofibroblast transformation (FMT) by significantly inhibiting transforming growth factor β1 (TGFβ1)-induced α-smooth muscle actin and type Ⅰ collagen expression. Previous studies suggested that heat shock protein 60 (HSP60) may be the target of celastrol. This study confirmed the direct interaction between celastrol and HSP60 through cellular thermal shift assay and surface plasmon resonance experiment, and demonstrated that the KD value of celastrol binding to HSP60 was 8.59 μmol·L-1. Further studies showed that knockdown of HSP60 promoted TGFβ1-induced FMT, especially in the medium and low dose TGFβ1 treatment group, and that the anti-FMT effect of celastrol was significantly weakened after HSP60 knockdown. These results indicated that HSP60 was involved in maintaining the resting state of fibroblasts, and the anti-FMT effect of celastrol was dependent on HSP60. Furthermore, the autophagy promotion and antioxidant effects of celastrol were also weakened after HSP60 knockdown. In conclusion, celastrol inhibits FMT by targeting HSP60, thus exerting anti-pulmonary fibrosis function.

celastrol  /  fibroblast  /  pulmonary fibrosis  /  heat shock protein 60  /  autophagy
Yu ZHOU, Ya-zi WEI, Tian-ming YANG, Tian-tai ZHANG. The target of celastrol acting on HSP60 against pulmonary fibrosis[J]. Acta Pharmaceutica Sinica, 2023 , 58 (3) : 688 -694 . DOI: 10.16438/j.0513-4870.2022-0983
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Article Info
doi: 10.16438/j.0513-4870.2022-0983
  • Receive Date：2022-08-09
  • Online Date：2025-11-21
  • Published：2023-03-12
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History
  • Received：2022-08-09
  • Revised：2022-09-30
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Affiliations
    1. State Key Laboratory of Bioactive Substance and Function of Nature Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China
    2. Tianjin Key Laboratory of Molecular Design and Drug Discovery, Tianjin Institute of Pharmaceutical Research, Tianjin 300301, China
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表12种不同金属材料的力学参数
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Family		 属数
Number of
genus		 种数
Number of
species		 占总种数比例
Percentage of
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Genus		 种数
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Percentage of total
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鹅膏菌科Amanitaceae 2 11 5.26 鹅膏菌属 Amanita 10 4.78
小菇科 Mycenaceae 2 12 5.74 丝盖伞属 Inocybe 5 2.39
多孔菌科 Polyporaceae 8 14 6.70 蜡蘑属 Laccaria 5 2.39
红菇科 Russulaceae 3 23 11.00 小皮伞属 Marasmius 6 2.87
小菇属 Mycena 11 5.26
光柄菇属 Pluteus 5 2.39
红菇属 Russula 17 8.13
栓菌属 Trametes 5 2.39
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