2021
DOI: 10.3389/fmolb.2021.645846
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Abstract: Idiopathic pulmonary fibrosis (IPF) is a distressing lung disorder with poor prognosis and high mortality rates. Limited therapeutic options for IPF is a major clinical challenge. Well-known for its anti-apoptotic properties, B-cell lymphoma 2 (Bcl-2) plays a critical role in the pathology of malignancies and inflammatory diseases, including IPF. In this study, we aimed to investigate the therapeutic effect of a Bcl-2 homology domain 3 mimetic inhibitor, ABT-199, on bleomycin (BLM)-induced pulmonary fibrosis i… Show more

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Cited by 5 publications
(2 citation statements)
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“…As fibrotic fibroblasts employ antiapoptotic BCL-2 family proteins to stay alive through the sequestration of proapoptotic activators, their priming status shifts, allowing them to become exquisitely sensitive to the effects of BH3 mimetics ( 24 , 27 , 41 , 42 ). BCL-2 inhibition with the BH3 mimetics have demonstrated efficacy in the single-dose bleomycin model to inhibit the development of fibrosis (if given during the inflammatory phase) and hasten spontaneous resolution of fibrosis (if given during the fibrotic phase) ( 26 , 43 , 44 ). However, because single-dose bleomycin is a model of homeostatic fibrosis resolution ( 6 , 8 , 12 ), it is a suboptimal model for studying fibroblast accumulation and resistance to apoptosis in the context of nonresolving lung disease, thus prompting our use of repetitive bleomycin and silicosis as models of persistent, progressive pulmonary fibrosis.…”
Section: Discussionmentioning
confidence: 99%
“…As fibrotic fibroblasts employ antiapoptotic BCL-2 family proteins to stay alive through the sequestration of proapoptotic activators, their priming status shifts, allowing them to become exquisitely sensitive to the effects of BH3 mimetics ( 24 , 27 , 41 , 42 ). BCL-2 inhibition with the BH3 mimetics have demonstrated efficacy in the single-dose bleomycin model to inhibit the development of fibrosis (if given during the inflammatory phase) and hasten spontaneous resolution of fibrosis (if given during the fibrotic phase) ( 26 , 43 , 44 ). However, because single-dose bleomycin is a model of homeostatic fibrosis resolution ( 6 , 8 , 12 ), it is a suboptimal model for studying fibroblast accumulation and resistance to apoptosis in the context of nonresolving lung disease, thus prompting our use of repetitive bleomycin and silicosis as models of persistent, progressive pulmonary fibrosis.…”
Section: Discussionmentioning
confidence: 99%
“…The in ammatory phase is the initial response of the body and is mediated by a variety of in ammatory cells. Multiple pro-in ammatory and brogenic cytokines and growth factors were found at 7 and 14 days [3,4],lung broblasts began to form at 14 days [5]and collagen deposition was signi cantly increased [6].A number of previous studies have shown that the activation and expansion of T cells in IPF patients play an important role in the progression of the disease. The role of the adaptive immune system in this process has been di cult to understand and highly controversial [7].T lymphocytes were represented by CD4,CD8 and regulatory T cells(Tregs),a subpopulation of T cells.The cytokine response of CD4 + cells has been examined in a number of studies of IPF patients.CD8 + cells were positively correlated with the severity of disease [8]and it also plays an important role in aseptic in ammatory repair/ brosis effector factors [9].The lower of CD4 + /CD8 + and the more CD8 + cells,the worse the response to treatment [10].Tregs have immunosuppressive effects that maintain immune tolerance and immune response homeostasis [11].In the BLM-induced pulmonary brosis mouse model,Tregs can accumulate in large quantities in lung tissue and worsen the disease.On the contrary,Tregs can also reduce pulmonary brosis by inhibiting in ammation and regulating the response of CD4 + helper T(Th)cells.Although it has been accepted that disturbed immune homeostasis plays a signi cant role in the pathogenesis and/or progression of IPF,the underlying mechanisms remains unclear [12].IPF patients have few effective treatment options beyond lung transplantation [13].So far,there are no effective drugs to treat the disease,it is crucial to nd possible therapeutic targets to treat IPF.…”
Section: Introductionmentioning
confidence: 99%