Molecular pathways in idiopathic pulmonary fibrosis pathogenesis: Transcending barriers to optimally targeted pharmacotherapies.
Molecular pathways in idiopathic pulmonary fibrosis pathogenesis: Transcending barriers to optimally targeted pharmacotherapies.
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DOI：
10.1016/j.ebiom.2021.103373
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发表时间：
2021-05
期刊：
影响因子：
11.1
通讯作者：
Adegunsoye A
中科院分区：
文献类型：
--
作者：
Strykowski R;Adegunsoye A
尽管特发性肺纤维化（IPF）患者的生存期中位数仍徘徊在两到五年左右，[1]但这种毁灭性间质性肺病的治疗前景受到缺乏有效药物疗法的阻碍。广泛使用的抗纤维化药物减缓了功能下降的速度[2，3]，但通常与不良反应和持续的高症状负担相关。由于纤维化的病理生理机制尚未完全阐明，我们对IPF疾病进展的理解仍然受到抑制，这对靶向这些机制的更多新型疗法可能获得的潜在价值构成了实质性限制。先前评估受影响患者遗传特征的全基因组相关研究已确定了与IPF发病机制相关的几种显著变异和风险多态性。[4]同样，最近的表观基因组学、转录组学和蛋白质组学数据有助于生成IPF的单细胞图谱，定义纤维化进展中的关键分子因素和途径。[5]其他组织病理学分析和免疫表型研究发现，IPF患者肺组织内存在表型不同的CD4+ T细胞浸润。[6]从宏观角度来看，最近的研究发现，从IPF患者获得的肺组织中的终末细支气管显著缺失，表明这种疾病涉及小气道。[7]总之，这些强调了进一步阐明这种复杂疾病的病理生理学的许多努力，其总体目标是确定最佳治疗靶点并改善目前存在的靶点。
Although the survival of patients with idiopathic pulmonary fibrosis (IPF) still hovers around a median of two to five years,[1] the therapeutic landscape of this devastating interstitial lung disease is encumbered by a paucity of effective pharmacotherapies. Widely used anti-fibrotic medications slow the rate of functional decline [2, 3] but are often associated with adverse effects and persistently high symptom burden. As the pathophysiologic mechanisms underlying fibrosis are yet to be fully elucidated, our understanding of disease progression in IPF remains stifled, posing substantial limitations to the potential value that could be gained from more novel therapies targeting these mechanisms. Prior genome-wide associated studies evaluating the genetic profiles of affected patients have identified several notable variants and risk polymorphisms associated with IPF pathogenesis.[4] Likewise, recent epigenomic, transcriptomic, and proteomic data have helped to generate a single-cell atlas of IPF defining key molecular factors and pathways in the progression of fibrosis.[5] Other histopathologic analyses and investigations focused on immunophenotyping have identified phenotypically distinct CD4+ T cell infiltrates within the lung tissue in patients with IPF.[6] From a macroscopic perspective, recent investigations have found a significant loss of terminal bronchioles in lung tissue obtained from patients with IPF, implicating the small airways in this disease.[7] Taken together, these underscore numerous efforts that further illuminate the pathophysiology of this complex disease, with the overall goal of identifying optimal therapeutic targets and improving currently existing ones.
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影响因子：
11.1
作者：
Xu F;Tanabe N;Vasilescu DM;McDonough JE;Coxson HO;Ikezoe K;Kinose D;Ng KW;Verleden SE;Wuyts WA;Vanaudenaerde BM;Verschakelen J;Cooper JD;Lenburg ME;Morshead KB;Abbas AR;Arron JR;Spira A;Hackett TL;Colby TV;Ryerson CJ;Ng RT;Hogg JC
通讯作者：
Hogg JC
影响因子：
7.3
作者：
Adegunsoye A;Hrusch CL;Bonham CA;Jaffery MR;Blaine KM;Sullivan M;Churpek MM;Strek ME;Noth I;Sperling AI
通讯作者：
Sperling AI
影响因子：
168.9
作者：
Noble, Paul W.;Albera, Carlo;du Bois, Roland M.
通讯作者：
du Bois, Roland M.
影响因子：
5.8
作者：
Tran, Tanja;Sterclova, Martina;Petkovic, Tatjana Radjenovic
通讯作者：
Petkovic, Tatjana Radjenovic
DOI：
10.1164/rccm.201905-1017oc
发表时间：
2020-03-01
影响因子：
24.7
作者：
Allen, Richard J.;Guillen-Guio, Beatriz;Wain, Louise, V
通讯作者：
Wain, Louise, V