Department of Pharmaceutical Sciences, Faculty of Life Sciences, University of Vienna, Vienna, Austria.
Institute of Physiology, Center for Physiology and Pharmacology, Medical University of Vienna, Vienna, Austria.
PLoS One. 2023 Feb 14;18(2):e0281191. doi: 10.1371/journal.pone.0281191. eCollection 2023.
We showed previously that capsaicin, an active compound of chili peppers, can inhibit platelet-derived growth factor-induced proliferation in primary rat vascular smooth muscle cells (VSMCs). The inhibition of BrdU incorporation by capsaicin in these cells was revoked by BCTC, which might be explained by a role of TRPV1 in VSMCs proliferation. To further pursue the hypothesis of a TRPV1-dependent effect of capsaicin, we investigated TRPV1 expression and function. Commercially available antibodies against two different TRPV1 epitopes (N-terminus and C-terminus) were rendered invalid in detecting TRPV1, as shown: i) in western blot experiments using control lysates of TRPV1-expressing (PC-12 and hTRPV1 transfected HEK293T) and TRPV1-downregulated (CRISPR/Cas gene edited A10) cells, and ii) by substantial differences in staining patterns between the applied antibodies using fluorescence confocal microscopy. The TRPV1 agonists capsaicin, resiniferatoxin, piperine and evodiamine did not increase intracellular calcium levels in primary VSMCs and in A10 cells. Using RT qPCR, we could detect a rather low TRPV1 expression in VSMCs at the mRNA level (Cp value around 30), after validating the primer pair in NGF-stimulated PC-12 cells. We conclude that rat vascular smooth muscle cells do not possess canonical TRPV1 channel activity, which could explain the observed antiproliferative effect of capsaicin.
我们之前已经表明,辣椒中的活性化合物辣椒素可以抑制血小板衍生生长因子诱导的原代大鼠血管平滑肌细胞(VSMCs)增殖。辣椒素对 BrdU 掺入的抑制作用可被 BCTC 逆转,这可能是 TRPV1 在 VSMCs 增殖中的作用所解释的。为了进一步验证辣椒素对 TRPV1 的依赖作用的假说,我们研究了 TRPV1 的表达和功能。针对两个不同 TRPV1 表位(N 端和 C 端)的商用抗体在检测 TRPV1 时变得无效,如以下所示:i)使用表达 TRPV1 的对照裂解物(PC-12 和转染 TRPV1 的 HEK293T)和 TRPV1 下调的细胞(CRISPR/Cas 基因编辑的 A10)进行 Western blot 实验,和 ii)通过荧光共聚焦显微镜使用应用抗体的染色模式存在显著差异。TRPV1 激动剂辣椒素、树脂毒素、胡椒碱和吴茱萸碱均不能增加原代 VSMCs 和 A10 细胞中的细胞内钙水平。使用 RT qPCR,我们可以在 VSMCs 的 mRNA 水平上检测到相当低的 TRPV1 表达(Cp 值约为 30),在 NGF 刺激的 PC-12 细胞中验证了引物对之后。我们得出结论,大鼠血管平滑肌细胞不具有典型的 TRPV1 通道活性,这可以解释观察到的辣椒素的抗增殖作用。