2. Academic Validation
  3. AAV9-HGF cooperating with TGF-beta/Smad inhibitor attenuates silicosis fibrosis via inhibiting ferroptosis

AAV9-HGF cooperating with TGF-beta/Smad inhibitor attenuates silicosis fibrosis via inhibiting ferroptosis

  • Biomed Pharmacother. 2023 Mar 16;161:114537. doi: 10.1016/j.biopha.2023.114537.
Rui Bao 1,  Qiushi Wang 1,  Mengxue Yu 1,  Yaling Zeng 2,  Shengpeng Wen 2,  Taiyang Liu 3,  Meng Wang 1,  Yuanyuan Li 1,  Sirong Chang 1,  Hongyang Chi 2,  Shengchao Ma 2,  Kai Wang 4,  Anning Yang 5,  Yideng Jiang 6,  Zhihong Liu 7,  Yue Sun 8
Affiliations

Affiliations

  • 1 School of Public Health and Management, General Hospital of Ningxia Medical University, Ningxia Medical University, Yinchuan 75000, Ningxia, China; NHC KEY Laboratory of Metabolic Cardiovascular Diseases Research, Ningxia Medical University, Yinchuan 75000, Ningxia, China; Key Laboratory of Environmental Factors and Chronic Disease Control, Yinchuan 750001, Ningxia, China.
  • 2 NHC KEY Laboratory of Metabolic Cardiovascular Diseases Research, Ningxia Medical University, Yinchuan 75000, Ningxia, China.
  • 3 Fuling Hospital, Chongqing University, 408000 Chongqing, China.
  • 4 School of Public Health and Management, General Hospital of Ningxia Medical University, Ningxia Medical University, Yinchuan 75000, Ningxia, China; Key Laboratory of Environmental Factors and Chronic Disease Control, Yinchuan 750001, Ningxia, China.
  • 5 School of Public Health and Management, General Hospital of Ningxia Medical University, Ningxia Medical University, Yinchuan 75000, Ningxia, China; NHC KEY Laboratory of Metabolic Cardiovascular Diseases Research, Ningxia Medical University, Yinchuan 75000, Ningxia, China; Key Laboratory of Environmental Factors and Chronic Disease Control, Yinchuan 750001, Ningxia, China. Electronic address: [email protected].
  • 6 School of Public Health and Management, General Hospital of Ningxia Medical University, Ningxia Medical University, Yinchuan 75000, Ningxia, China; NHC KEY Laboratory of Metabolic Cardiovascular Diseases Research, Ningxia Medical University, Yinchuan 75000, Ningxia, China; Key Laboratory of Environmental Factors and Chronic Disease Control, Yinchuan 750001, Ningxia, China. Electronic address: [email protected].
  • 7 School of Public Health and Management, General Hospital of Ningxia Medical University, Ningxia Medical University, Yinchuan 75000, Ningxia, China; NHC KEY Laboratory of Metabolic Cardiovascular Diseases Research, Ningxia Medical University, Yinchuan 75000, Ningxia, China; Key Laboratory of Environmental Factors and Chronic Disease Control, Yinchuan 750001, Ningxia, China. Electronic address: [email protected].
  • 8 School of Public Health and Management, General Hospital of Ningxia Medical University, Ningxia Medical University, Yinchuan 75000, Ningxia, China; NHC KEY Laboratory of Metabolic Cardiovascular Diseases Research, Ningxia Medical University, Yinchuan 75000, Ningxia, China; Key Laboratory of Environmental Factors and Chronic Disease Control, Yinchuan 750001, Ningxia, China. Electronic address: [email protected].
PMID: 36933378 DOI: 10.1016/j.biopha.2023.114537
Abstract

Silicosis is a devastating interstitial lung disease characterized by silicon nodules and diffuse pulmonary fibrosis. To date, inefficient therapy is still a challenge of this disease due to its complicated pathogenesis. Hepatocyte growth factor (HGF) which is highly expressed in hepatocyte with anti-fibrotic and anti-apoptotic function was downregulated in silicosis. In addition, the upregulation of transforming growth factor-beta (TGF-β), another pathological molecular was observed to aggravate the severity and accelerate the progression of silicosis. Here AAV expressed HGF with targeting pulmonary capillaries and SB431542, the inhibitor of TGF-β signal pathway, were simultaneously adopted to synergistically reduce silicosis fibrosis. In vivo result demonstrated that the cooperation of HGF with SB431542 showed strong anti-fibrosis effects on the silicosis mice via tracheal administration of silica, compared to the separate treatment. The high efficacy was mainly achieved by remarkably by reducing Ferroptosis of lung tissue. In our point, the combination of AAV9-HGF with SB431542 provide an alternative to relieve silicosis fibrosis from the perspective of targeting pulmonary capillaries.

Keywords

Adeno-associated virus; Ferroptosis; HGF; SB431542; Silicosis.

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