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肾福康胶囊通过STAT3/YAP通路调控细胞串扰改善肾间质纤维化的机制
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| 篇名： | 肾福康胶囊通过STAT3/YAP通路调控细胞串扰改善肾间质纤维化的机制 |
| TITLE： | Mechanism of Shenfukang capsule in ameliorating renal interstitial fibrosis by regulating cellular crosstalk via the STAT3/YAP pathway |
| 摘要： | 目的 探讨肾福康胶囊（SFK）通过信号转导及转录活化因子3（STAT3）/Yes相关蛋白（YAP）通路调控巨噬细胞-成纤维细胞串扰改善肾间质纤维化（RIF）的作用机制。方法用转化生长因子β（1TGF-β1）诱导巨噬细胞RAW264.7极化，再建立巨噬细胞与肾成纤维细胞NRK-49F的非接触共培养体系，以及巨噬细胞与YAP敲低肾成纤维细胞非接触共培养体系，给予低、中、高浓度（4、8、16μg/mL）SFK，以及STAT3抑制剂（STAT3-I，1.64μg/mL）、氯沙坦钾片（阳性对照，0.28μg/mL），干预48h。检测巨噬细胞中CD86、CD163、STAT3蛋白和CD86、F4/80、STAT3mRNA表达水平，共培养肾成纤维细胞中α平滑肌肌动蛋白（α-SMA）、波形蛋白（Vimentin）、Ⅰ型胶原（Col-Ⅰ）、基质金属蛋白酶1（MMP-1）、YAP蛋白及mRNA表达水平，以及共培养YAP敲低肾成纤维细胞中α-SMA、Vimentin、MMP-1蛋白及mRNA表达水平。结果TGF-β1诱导后巨噬细胞中CD86、CD163、STAT3蛋白表达水平和CD86、F4/80、STAT3mRNA表达水平均显著升高（P＜0.05）；极化的巨噬细胞的培养液可激活肾成纤维细胞，使肾成纤维细胞中α-SMA、Vimentin、Col-Ⅰ、YAP蛋白及mRNA表达水平均显著升高，MMP-1蛋白及mRNA表达水平显著降低（P＜0.05）；SFK、STAT3-I可逆转以上指标的变化，其中SFK中浓度组部分指标效果强于SFK低、高浓度组。在巨噬细胞与YAP敲低肾成纤维细胞非接触共培养实验中，各组细胞中α-SMA、Vimentin、MMP-1蛋白及mRNA表达差异均无统计学意义。结论SFK可通过阻断STAT3/YAP通路，抑制巨噬细胞-肾成纤维细胞串扰，从而延缓RIF进展。 |
| ABSTRACT： | OBJECTIVE To investigate the mechanism by which Shenfukang capsule （SFK） ameliorates renal interstitial fibrosis （RIF） by regulating macrophage-fibroblast crosstalk via the signal transducer and activator of transcription 3 （STAT3）/Yes-associated protein （YAP） pathway. METHODS RAW264.7 macrophages were induced to polarize with transforming growth factor-β 1 （TGF-β 1 ）. Subsequently， a non-contact co-culture system of macrophages with renal fibroblasts NRK-49F， as well as a non-contact co-culture system of macrophages with YAP-knockdown renal fibroblasts， were established. Cells were treated with low， medium， and high concentrations （4， 8， 16 μg/mL） of SFK， as well as a STAT3 inhibitor （STAT3-I，1.64 μg/mL） and losartan potassium tablets （positive control， 0.28 μg/mL）， for 48 h. After intervention， the protein and mRNA expression levels of CD86， CD163， and STAT3 in macrophages， as well as CD86， F4/80， and STAT3 mRNA， were detected. In co-cultured renal fibroblasts， the protein and mRNA expression levels of α -smooth muscle actin （ α -SMA）， Vimentin， collagen type Ⅰ （Col-Ⅰ）， matrix metalloproteinase-1 （MMP-1）， and YAP were detected. In co-cultured YAP-knockdown renal fibroblasts， the protein and mRNA expression levels of α -SMA， Vimentin， and MMP-1 were also detected. RESULTS Following TGF-β 1 induction， the protein expression levels of CD86， CD163， and STAT3， as well as the mRNA expression levels of CD86， F4/80， and STAT3 in macrophages were significantly increased （ P ＜0.05）. The conditioned medium from polarized macrophages activated renal fibroblasts， as evidenced by significantly increased protein and mRNA expression levels of α -SMA， Vimentin， Col-Ⅰ， and YAP， and significantly decreased protein and mRNA expression levels of MMP-1 in renal fibroblasts （ P ＜0.05）. Treatment with SFK and STAT3-I reversed the changes in the above indicators， with the medium concentration SFK group showing stronge r effects on some indicators than the low and high concentration groups. In the non-contact co-culture experiment of macrophages and YAP-knockdown renal fibroblasts， there were no statistically significant differences in the protein and mRNA expression of α-SMA， Vimentin， and MMP-1 among the groups. CONCLUSIONS SFK can inhibit macrophage-renal fibroblast crosstalk by blocking the STAT3/YAP pathway， thereby delaying the progression of RIF. |
| 期刊： | 2026年第37卷第12期 |
| 作者： | 杜炜；杨玉芳；廖燕红；邹小琴；梁志伟；冯祥乾；钟小斌 |
| AUTHORS： | DU Wei， YANG Yufang，LIAO Yanhong，ZOU Xiaoqin，LIANG Zhiwei，FENG Xiangqian，ZHONG Xiaobin |
| 关键字： | 肾福康胶囊; 肾间质纤维化; 巨噬细胞; 成纤维细胞; 细胞串扰; STAT3/YAP通路 |
| KEYWORDS： | Shenfukang capsule; renal interstitial fibrosis; macrophage; fibroblast; cellular crosstalk; STAT3/YAP pathway |
| 阅读数： | 1 次 |
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