成纤维细胞MrgprX2/B2信号传导驱动增生性瘢痕纤维化
Fibroblast MrgprX2/B2 signaling drives hypertrophic scar fibrosis.
摘要(中文译文)
增生性瘢痕（HTS）是一种常见的临床难题，以成纤维细胞过度活化和组织纤维化为特征。然而，驱动病理性成纤维细胞增殖的上游信号仍知之甚少。在此，我们鉴定出传统上局限于肥大细胞的G蛋白偶联受体MrgprX2（人）/MrgprB2（小鼠），在HTS进展过程中作为真皮成纤维细胞中可诱导的促纤维化受体。MrgprX2在HTS来源的真皮成纤维细胞中显著上调，且药理学抑制MrgprX2可显著减轻人源化皮肤类器官模型中的纤维化。在小鼠研究中，内源性肽LL37作为成纤维细胞中MrgprX2/B2的激活剂出现，触发钙内流、转化生长因子β1（TGF-β1）分泌及增殖。成纤维细胞中MrgprB2的基因敲除显著减轻了体内纤维化，确立了LL37-MrgprX2/B2-TGF-β1轴作为成纤维细胞活化和纤维化重塑的关键介质。总之，我们的研究结果将MrgprX2/B2定位为组织损伤相关信号与纤维化病理之间的关键分子纽带，为HTS中成纤维细胞驱动的纤维化提供了有前景的治疗靶点。
Abstract
Hypertrophic scarring (HTS) represents a common clinical challenge characterized by excessive fibroblast activation and tissue fibrosis. However, the upstream signals driving pathological fibroblast proliferation remain poorly understood. Here, we identify the G protein-coupled receptor MrgprX2 (human)/MrgprB2 (mouse), traditionally restricted to mast cells, as an inducible pro-fibrotic receptor in dermal fibroblasts during HTS progression. MrgprX2 is markedly upregulated in dermal fibroblasts from HTS, and pharmacological inhibition of MrgprX2 significantly reduces fibrosis in humanized skin organoid models. In mouse studies, the endogenous peptide LL37 emerged as an MrgprX2/B2 activator in fibroblasts, triggering calcium influx, transforming growth factor β1 (TGF-β1) secretion, and proliferation. Genetic ablation of MrgprB2 in fibroblasts significantly reduced fibrosis in vivo, establishing the LL37-MrgprX2/B2-TGF-β1 axis as a key mediator of fibroblast activation and fibrotic remodeling. Together, our findings position MrgprX2/B2 as a critical molecular link between tissue injury-associated signals and fibrotic pathology, offering a promising therapeutic target for fibroblast-driven fibrosis in HTS.
如何引用
AMA
Heng Xu, Meiying Sheng, Yuxin Jia, Yi Luo, Liyan Wu, Luxian Zhou, et al. Fibroblast MrgprX2/B2 signaling drives hypertrophic scar fibrosis.. Cell reports. 2026; doi:10.1016/j.celrep.2026.117616.
APA
Heng Xu, Meiying Sheng, Yuxin Jia, Yi Luo, Liyan Wu, Luxian Zhou, et al (2026). Fibroblast MrgprX2/B2 signaling drives hypertrophic scar fibrosis.. Cell reports. https://doi.org/10.1016/j.celrep.2026.117616
GB/T 7714
Heng Xu, Meiying Sheng, Yuxin Jia, Yi Luo, Liyan Wu, Luxian Zhou, et al. Fibroblast MrgprX2/B2 signaling drives hypertrophic scar fibrosis.[J]. Cell reports, 2026 doi:10.1016/j.celrep.2026.117616.
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