Baicalin inhibits cell apoptosis, inflammation and ferroptosis in ulcerative colitis by influencing SP1-mediated transcription of SLC6A14.

IF 2.7 3区医学 Q2 CRITICAL CARE MEDICINE

SHOCK Pub Date : 2025-03-20 DOI:10.1097/SHK.0000000000002587

Huifang Sun, Lijuan Hu, Peipei Hao, Yawei Liu, Ying Tian

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Abstract

Abstract: Background: Baicalin is considered to be able to alleviate the progression of ulcerative colitis (UC), but the underlying molecular mechanism needs to be further elucidated.Methods: TNF-α-induced human normal colorectal mucosa cells (FHC) were used to mimic UC models in vitro, and trinitrobenzene sulfonic acid (TNBS)-injected rats were used to construct UC models in vivo. Cell proliferation and apoptosis were determined by CCK8 assay, EdU assay and flow cytometry. Inflammation factors were examined by ELISA, and ferroptosis-related markers were detected by corresponding kit. The mRNA and protein levels of solute carrier family 6 member 14 (SLC6A14) and specific protein 1 (SP1) were analyzed by qRT-PCR and western blot. The interaction between SP1 and SLC6A14 promoter was verified by ChIP assay and dual-luciferase reporter assay.Results: Baicalin enhanced proliferation, while repressed apoptosis, inflammation and ferroptosis in TNF-α-induced FHC cells. SLC6A14 was upregulated in UC patients, and baicalin could decrease SLC6A14 expression. SLC6A14 overexpression reversed the inhibitory effect of baicalin on TNF-α-induced FHC cell injury. SP1 could bind to SLC6A14 promoter region to upregulate its expression, and ectopic expression of SLC6A14 also abolished the suppressive effect of SP1 knockdown on TNF-α-induced FHC cell injury. Baicalin reduced SP1 expression to downregulate SLC6A14. Also, baicalin alleviated UC process in vivo via repressing inflammation and ferroptosis.Conclusion: Baicalin repressed SP1-mediated transcription of SLC6A14 to restrain cell apoptosis, inflammation and ferroptosis, thus alleviating UC progression.

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黄芩苷通过影响sp1介导的SLC6A14转录抑制溃疡性结肠炎细胞凋亡、炎症和铁凋亡。

摘要：背景：黄芩苷被认为能够缓解溃疡性结肠炎（UC）的进展，但其潜在的分子机制有待进一步阐明。方法：采用TNF-α-诱导的人正常结肠粘膜细胞（FHC）体外模拟UC模型，采用三硝基苯磺酸（TNBS）注射大鼠体内构建UC模型。CCK8法、EdU法和流式细胞术检测细胞增殖和凋亡。ELISA检测炎症因子，试剂盒检测凋亡相关标志物。采用qRT-PCR和western blot分析溶质载体家族6成员14 （SLC6A14）和特异性蛋白1 （SP1）的mRNA和蛋白水平。SP1与SLC6A14启动子的相互作用通过ChIP实验和双荧光素酶报告基因实验验证。结果：黄芩苷促进TNF-α-诱导的FHC细胞增殖，抑制凋亡、炎症和铁凋亡。SLC6A14在UC患者中表达上调，黄芩苷可降低SLC6A14的表达。SLC6A14过表达逆转了黄芩苷对TNF-α-诱导的FHC细胞损伤的抑制作用。SP1可结合SLC6A14启动子区上调其表达，SLC6A14的异位表达也可消除SP1敲低对TNF-α-诱导的FHC细胞损伤的抑制作用。黄芩苷降低SP1表达下调SLC6A14。此外，黄芩苷通过抑制炎症和铁下垂来减轻体内UC过程。结论：黄芩苷通过抑制sp1介导的SLC6A14转录，抑制细胞凋亡、炎症和铁下沉，从而缓解UC的进展。

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来源期刊

SHOCK 医学-外科

CiteScore

6.20

自引率

3.20%

发文量

199

审稿时长

1 months

期刊介绍： SHOCK®: Injury, Inflammation, and Sepsis: Laboratory and Clinical Approaches includes studies of novel therapeutic approaches, such as immunomodulation, gene therapy, nutrition, and others. The mission of the Journal is to foster and promote multidisciplinary studies, both experimental and clinical in nature, that critically examine the etiology, mechanisms and novel therapeutics of shock-related pathophysiological conditions. Its purpose is to excel as a vehicle for timely publication in the areas of basic and clinical studies of shock, trauma, sepsis, inflammation, ischemia, and related pathobiological states, with particular emphasis on the biologic mechanisms that determine the response to such injury. Making such information available will ultimately facilitate improved care of the traumatized or septic individual.