Melanocortin therapies to resolve fibroblast-mediated diseases.
Melanocortin therapies to resolve fibroblast-mediated diseases.
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黑色皮质素疗法可以解决成纤维细胞介导的疾病。
DOI：
10.3389/fimmu.2022.1084394
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发表时间：
2022
影响因子：
7.3
通讯作者：
Montero-Melendez, Trinidad
中科院分区：
文献类型：
--
作者：
Khodeneva, Natalya;Sugimoto, Michelle A.;Davan-Wetton, Camilla S. A.;Montero-Melendez, Trinidad
基质细胞已成为多种疾病的核心驱动因素，因此，作为开发新型治疗策略的潜在新细胞靶点。在这篇综述中，我们修正了成纤维细胞的主要作用，不仅作为结构细胞，而且作为免疫反应的参与者和调节剂。重要的方面，如成纤维细胞异质性，功能特化和细胞可塑性也被讨论，以及这些方面可能在疾病和新疗法的设计中的意义。对成纤维细胞在不同条件下的作用的广泛修订揭示了这种细胞类型在许多疾病中起致病性作用的存在，或由于其“结构”方面的加剧，或由于其“免疫方面”的失调。在这两种情况下，发展创新治疗方法的机会是存在的。在这方面，我们修改了现有的证据，指出黑素皮质素途径是治疗和管理由异常活化的成纤维细胞介导的疾病的潜在新策略，包括硬皮病或类风湿关节炎。这一证据来自于涉及体外原代成纤维细胞模型、体内疾病模型以及正在进行的人体临床试验的研究。作为促溶解介质的黑素皮质素药物，已显示出减少胶原沉积、激活肌成纤维细胞、减少促炎介质和减少疤痕形成的能力。在这里，我们还讨论了现有的挑战，包括将成纤维细胞作为治疗靶点，以及开发新的黑素皮质素候选药物，这可能有助于推进该领域的发展，并为高医疗需求疾病的管理提供新药。
Stromal cells have emerged as central drivers in multiple and diverse diseases, and consequently, as potential new cellular targets for the development of novel therapeutic strategies. In this review we revise the main roles of fibroblasts, not only as structural cells but also as players and regulators of immune responses. Important aspects like fibroblast heterogeneity, functional specialization and cellular plasticity are also discussed as well as the implications that these aspects may have in disease and in the design of novel therapeutics. An extensive revision of the actions of fibroblasts on different conditions uncovers the existence of numerous diseases in which this cell type plays a pathogenic role, either due to an exacerbation of their 'structural' side, or a dysregulation of their 'immune side'. In both cases, opportunities for the development of innovative therapeutic approaches exist. In this regard, here we revise the existing evidence pointing at the melanocortin pathway as a potential new strategy for the treatment and management of diseases mediated by aberrantly activated fibroblasts, including scleroderma or rheumatoid arthritis. This evidence derives from studies involving models of in vitro primary fibroblasts, in vivo models of disease as well as ongoing human clinical trials. Melanocortin drugs, which are pro-resolving mediators, have shown ability to reduce collagen deposition, activation of myofibroblasts, reduction of pro-inflammatory mediators and reduced scar formation. Here we also discuss existing challenges, both in approaching fibroblasts as therapeutic targets, and in the development of novel melanocortin drug candidates, that may help advance the field and deliver new medicines for the management of diseases with high medical needs.
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影响因子：
6
作者：
Chu J;Lu M;Pfeifer CG;Alt V;Docheva D
通讯作者：
Docheva D
影响因子：
3
作者：
Joseph CG;Yao H;Scott JW;Sorensen NB;Marnane RN;Mountjoy KG;Haskell-Luevano C
通讯作者：
Haskell-Luevano C
影响因子：
6.5
作者：
Berberich, Bettina;Thriene, Kerstin;Dengjel, Joern
通讯作者：
Dengjel, Joern
DOI：
10.1146/annurev-pathol-121808-102144
发表时间：
2010
期刊：
Annual review of pathology
影响因子：
--
作者：
Coppé JP;Desprez PY;Krtolica A;Campisi J
通讯作者：
Campisi J
影响因子：
16.8
作者：
Buckley, CD;Pilling, D;Salmon, M
通讯作者：
Salmon, M