Mechanosensing by TRPV4 mediates stiffness-induced foreign body response and giant cell formation.
Mechanosensing by TRPV4 mediates stiffness-induced foreign body response and giant cell formation.
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DOI：
10.1126/scisignal.abd4077
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发表时间：
2021-11-02
影响因子：
7.3
通讯作者：
Rahaman, Shaik O.
中科院分区：
文献类型：
--
作者：
Goswami, Rishov;Arya, Rakesh K.;Sharma, Shweta;Dutta, Bidisha;Stamov, Dimitar R.;Zhu, Xiaoping;Rahaman, Shaik O.
将生物材料或器械植入软组织通常会导致异物反应（FBR），这是一种可导致植入物失效、组织损伤和患者死亡的炎症性疾病。巨噬细胞积聚并融合，在组织-植入物界面产生破坏性异物巨细胞（FBGC），导致肌成纤维细胞产生的植入物周围纤维瘢痕组织的发展。我们以前表明，体内FBR和体外FBGC的形成需要瞬时受体电位香草酸4（TRPV 4），一个机械敏感的离子通道。在这里，我们报告说，TRPV 4是专门为FBR所需的植入刚度独立的生化线索和细胞内硬化，促进FBGC形成体外诱导的。TRPV 4缺乏减少胶原沉积和巨噬细胞，FBGC和肌成纤维细胞的积累，在硬，但不软，植入物在体内和抑制巨噬细胞诱导的野生型成纤维细胞分化成肌成纤维细胞在体外。原子力显微镜表明，TRPV 4是所需的种植体附近的组织硬化在体内和细胞骨架重塑和细胞内硬化诱导的融合细胞因子在体外。总之，这些数据表明了一种机制，即TRPV 4和底物刚度之间的相互作用导致细胞骨架重塑和细胞力产生，以促进FBR期间FBGC的形成。
Implantation of biomaterials or devices into soft tissue often leads to the development of the foreign body response (FBR), an inflammatory condition that can cause implant failure, tissue injury, and death of the patient. Macrophages accumulate and fuse to generate destructive foreign body giant cells (FBGCs) at the tissue-implant interface, leading to the development of fibrous scar tissue around the implant that is generated by myofibroblasts. We previously showed that the FBR in vivo and FBGC formation in vitro require transient receptor potential vanilloid 4 (TRPV4), a mechanosensitive ion channel. Here, we report that TRPV4 was required specifically for the FBR induced by implant stiffness independently of biochemical cues and for intracellular stiffening that promotes FBGC formation in vitro. TRPV4 deficiency reduced collagen deposition and the accumulation of macrophages, FBGCs, and myofibroblasts at stiff, but not soft, implants in vivo and inhibited macrophage-induced differentiation of wild-type fibroblasts into myofibroblasts in vitro. Atomic force microscopy demonstrated that TRPV4 was required for implant-adjacent tissue stiffening in vivo and for cytoskeletal remodeling and intracellular stiffening induced by fusogenic cytokines in vitro. Together, these data suggest a mechanism whereby a reciprocal functional interaction between TRPV4 and substrate stiffness leads to cytoskeletal remodeling and cellular force generation to promote FBGC formation during the FBR.
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影响因子：
3.5
作者：
Gavara N;Chadwick RS
通讯作者：
Chadwick RS
影响因子：
5
作者：
Adapala RK;Thoppil RJ;Luther DJ;Paruchuri S;Meszaros JG;Chilian WM;Thodeti CK
通讯作者：
Thodeti CK
影响因子：
--
作者：
Fereol, Sophie;Fodil, Redouane;Planus, Emmanuelle
通讯作者：
Planus, Emmanuelle
DOI：
10.1007/978-3-642-54215-2_12
发表时间：
2014-01-01
期刊：
MAMMALIAN TRANSIENT RECEPTOR POTENTIAL (TRP) CATION CHANNELS, VOL I
影响因子：
--
作者：
Garcia-Elias, Anna;Mrkonjic, Sanela;Valverde, Miguel A.
通讯作者：
Valverde, Miguel A.
DOI：
10.1073/pnas.1005333107
发表时间：
2010-11-02
影响因子：
11.1
作者：
Everaerts, Wouter;Zhen, Xiaoguang;Voets, Thomas
通讯作者：
Voets, Thomas