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10.1126/sciadv.abb6075

http://scihub22266oqcxt.onion/10.1126/sciadv.abb6075
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33277324!7775789!33277324
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suck abstract from ncbi


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pmid33277324      Sci+Adv 2021 ; 7 (1): ä
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  • MBD2 serves as a viable target against pulmonary fibrosis by inhibiting macrophage M2 program #MMPMID33277324
  • Wang Y; Zhang L; Wu GR; Zhou Q; Yue H; Rao LZ; Yuan T; Mo B; Wang FX; Chen LM; Sun F; Song J; Xiong F; Zhang S; Yu Q; Yang P; Xu Y; Zhao J; Zhang H; Xiong W; Wang CY
  • Sci Adv 2021[Jan]; 7 (1): ä PMID33277324show ga
  • Despite past extensive studies, the mechanisms underlying pulmonary fibrosis (PF) still remain poorly understood. Here, we demonstrated that lungs originating from different types of patients with PF, including coronavirus disease 2019, systemic sclerosis-associated interstitial lung disease, and idiopathic PF, and from mice following bleomycin (BLM)-induced PF are characterized by the altered methyl-CpG-binding domain 2 (MBD2) expression in macrophages. Depletion of Mbd2 in macrophages protected mice against BLM-induced PF. Mbd2 deficiency significantly attenuated transforming growth factor-beta1 (TGF-beta1) production and reduced M2 macrophage accumulation in the lung following BLM induction. Mechanistically, Mbd2 selectively bound to the Ship promoter in macrophages, by which it repressed Ship expression and enhanced PI3K/Akt signaling to promote the macrophage M2 program. Therefore, intratracheal administration of liposomes loaded with Mbd2 siRNA protected mice from BLM-induced lung injuries and fibrosis. Together, our data support the possibility that MBD2 could be a viable target against PF in clinical settings.
  • |Animals[MESH]
  • |Bleomycin/pharmacology[MESH]
  • |COVID-19/*metabolism[MESH]
  • |Carcinoma, Non-Small-Cell Lung/metabolism[MESH]
  • |DNA-Binding Proteins/*metabolism[MESH]
  • |Fibrosis[MESH]
  • |Gene Expression Profiling[MESH]
  • |Gene Expression Regulation[MESH]
  • |Humans[MESH]
  • |Liposomes/chemistry[MESH]
  • |Lung Diseases, Interstitial/metabolism[MESH]
  • |Lung Neoplasms/metabolism[MESH]
  • |Macrophages/*metabolism/virology[MESH]
  • |Male[MESH]
  • |Mice[MESH]
  • |Mice, Inbred C57BL[MESH]
  • |Mice, Knockout[MESH]
  • |Pulmonary Fibrosis/*metabolism/virology[MESH]
  • |RNA, Small Interfering/metabolism[MESH]
  • |Scleroderma, Systemic/metabolism[MESH]
  • |Signal Transduction[MESH]


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