Corrigendum: IL-13 mediates collagen deposition via STAT6 and microRNA-135b: a role for epigenetics.
Corrigendum: IL-13 mediates collagen deposition via STAT6 and microRNA-135b: a role for epigenetics.
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DOI：
10.1038/srep27325
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发表时间：
2016-06-10
影响因子：
4.6
通讯作者：
van Laar JM
中科院分区：
文献类型：
--
作者：
O'Reilly S;Ciechomska M;Fullard N;Przyborski S;van Laar JM
系统性硬化症是一种自身免疫性结缔组织病，T细胞在其中起重要作用。我们和其他人之前已经证明了T细胞来源的IL-13在介导真皮成纤维细胞胶原诱导中的作用，用IL-13抗体阻断可以抑制这种增加。在这项研究中，我们想要探索支持IL-13介导的基质沉积的信号。分离的真皮成纤维细胞与重组IL-13共同孵育，定量逆转录聚合酶链式反应检测胶原1A1和转化生长因子-β1的基因表达。将miR-135B分别转染成纤维细胞和IL-13细胞，观察miR在成纤维细胞中的作用。从患者分离的系统性硬化症成纤维细胞和血清中检测到MIR-135B。结果表明，IL-13促进了胶原的表达，并且这一作用不依赖于转化生长因子-β-1。这依赖于STAT6作为这种被阻断的诱导的靶点。MIR-135B减少成纤维细胞的胶原诱导，硬皮病成纤维细胞具有较低的miR组成水平。我们进一步证明miR135b被甲基化抑制，并可能包括MeCP2。综上所述，我们发现STAT6和miR-135B调节成纤维细胞IL-13介导的胶原合成。
Systemic sclerosis is an autoimmune connective tissue disease in which T cells play a prominent role. We and others have previously demonstrated a role for T cell-derived IL-13 in mediating the induction of collagen in dermal fibroblasts and that blockade with IL-13 antibodies attenuates this increase. In this study we want to probe the signalling that underpins IL-13 mediated matrix deposition. Isolated dermal fibroblasts were incubated with recombinant IL-13 and gene expression by qRT-PCR was performed for collagen1A1 and TGF-β1. Small interfering RNA (siRNA) was used to knock down STAT6 and a small molecule inhibitor was also used to block this pathway. MiR-135b was transfected into fibroblasts plus and minus IL-13 to see if this miR plays a role. miR-135b was measured in systemic sclerosis fibroblasts isolated from patients and also in serum. Results showed that IL-13 increased collagen expression and that this is independent from TGF-β1. This is dependent on STAT6 as targeting this blocked induction. MiR-135b reduces collagen induction in fibroblasts and scleroderma fibroblasts have lower constitutive levels of the miR. We further demonstrate that miR135b is repressed by methylation and may include MeCP2. In conclusion we show that STAT6 and miR-135b regulate IL-13-mediated collagen production by fibroblasts.