Chlorogenic Acid Alleviates Non‐Alcoholic Steatohepatitis via Suppressing Liver Inflammatory Injury by Targeting Transforming Growth Factor Beta Receptor‐1 in Liver Sinusoidal Endothelial Cells
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Wiley
2025
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| author | Hao Ouyang Hui Miao Hong Zhang Bin Lu Jinyu Zhang Tianyu Zhang Junfeng Zhu Zhengtao Wang Lili Ji |
| author_facet | Hao Ouyang Hui Miao Hong Zhang Bin Lu Jinyu Zhang Tianyu Zhang Junfeng Zhu Zhengtao Wang Lili Ji Hao Ouyang Hui Miao Hong Zhang Bin Lu Jinyu Zhang Tianyu Zhang Junfeng Zhu Zhengtao Wang Lili Ji |
| collection | Wiley Open Access |
| contents | Chlorogenic Acid Alleviates Non‐Alcoholic Steatohepatitis via Suppressing Liver Inflammatory Injury by Targeting Transforming Growth Factor Beta Receptor‐1 in Liver Sinusoidal Endothelial Cells Hao Ouyang Hui Miao Hong Zhang Bin Lu Jinyu Zhang Tianyu Zhang Junfeng Zhu Zhengtao Wang Lili Ji Phytotherapy Research ABSTRACT Increasing evidence indicates that liver sinusoidal endothelial cells (LSECs) are crucial for non‐alcoholic steatohepatitis (NASH) development. Based on chlorogenic acid (CGA), which can improve NASH, this study aims to investigate the concrete mechanism of LSECs in NASH progression and identify CGA's key target in LSECs. High‐fat diet and methionine and choline deficient diet were used to induce NASH in mice. Western blot detecting endothelial molecules' expression, leukostasis assay, and Evans blue leakage were conducted to observe hepatic endothelial barrier dysfunction. Cell adhesion, transendothelial migration (TEM), and transendothelial electrical resistance were performed. Biotin pull‐down, cellular thermal shift assay, and surface plasmon resonance were used to identify CGA's key target. The pivotal roles of TGF β R1 and ID1 were investigated using adeno‐associated virus, plasmid, siRNA, or chemical inhibitor. CGA decreased ID1 expression by binding to TGF β R1 in LSECs, thereby reversing the change of hepatic vascular phenotype and abrogating hepatic infiltration of inflammatory cells during NASH progression. ID1 knockdown alleviated liver inflammation via suppressing TEM of inflammatory cells through reversing endothelial barrier dysfunction. However, TGF β R1 or ID1 overexpression reversed the CGA‐provided amelioration of liver inflammatory injury and endothelial barrier disorder. The decreased ID1 reduced NF κ B‐initiated VCAM1 and ICAM1 expression and weakened ID1's inhibition on HIF1 α ‐mediated VE‐Cad expression, thereby maintaining hepatic endothelium homeostasis. LSECs are crucial for the progression of liver steatosis into NASH, and CGA alleviated liver inflammatory injury during NASH progression by inhibiting ID1‐initiated NF κ B and HIF1 α signaling pathways through binding to TGF β R1 in LSECs. 10.1002/ptr.70095 http://onlinelibrary.wiley.com/termsAndConditions#vor |
| doi_str_mv | 10.1002/ptr.70095 |
| format | Artículo Open Access |
| id | wiley_oa_10_1002_ptr_70095 |
| institution | Wiley Open Access |
| license_str_mv | http://onlinelibrary.wiley.com/termsAndConditions#vor |
| publishDate | 2025 |
| publisher | Wiley |
| record_format | wiley_oa |
| spellingShingle | Chlorogenic Acid Alleviates Non‐Alcoholic Steatohepatitis via Suppressing Liver Inflammatory Injury by Targeting Transforming Growth Factor Beta Receptor‐1 in Liver Sinusoidal Endothelial Cells Hao Ouyang Hui Miao Hong Zhang Bin Lu Jinyu Zhang Tianyu Zhang Junfeng Zhu Zhengtao Wang Lili Ji Phytotherapy Research Chlorogenic Acid Alleviates Non‐Alcoholic Steatohepatitis via Suppressing Liver Inflammatory Injury by Targeting Transforming Growth Factor Beta Receptor‐1 in Liver Sinusoidal Endothelial Cells Hao Ouyang Hui Miao Hong Zhang Bin Lu Jinyu Zhang Tianyu Zhang Junfeng Zhu Zhengtao Wang Lili Ji Phytotherapy Research ABSTRACT Increasing evidence indicates that liver sinusoidal endothelial cells (LSECs) are crucial for non‐alcoholic steatohepatitis (NASH) development. Based on chlorogenic acid (CGA), which can improve NASH, this study aims to investigate the concrete mechanism of LSECs in NASH progression and identify CGA's key target in LSECs. High‐fat diet and methionine and choline deficient diet were used to induce NASH in mice. Western blot detecting endothelial molecules' expression, leukostasis assay, and Evans blue leakage were conducted to observe hepatic endothelial barrier dysfunction. Cell adhesion, transendothelial migration (TEM), and transendothelial electrical resistance were performed. Biotin pull‐down, cellular thermal shift assay, and surface plasmon resonance were used to identify CGA's key target. The pivotal roles of TGF β R1 and ID1 were investigated using adeno‐associated virus, plasmid, siRNA, or chemical inhibitor. CGA decreased ID1 expression by binding to TGF β R1 in LSECs, thereby reversing the change of hepatic vascular phenotype and abrogating hepatic infiltration of inflammatory cells during NASH progression. ID1 knockdown alleviated liver inflammation via suppressing TEM of inflammatory cells through reversing endothelial barrier dysfunction. However, TGF β R1 or ID1 overexpression reversed the CGA‐provided amelioration of liver inflammatory injury and endothelial barrier disorder. The decreased ID1 reduced NF κ B‐initiated VCAM1 and ICAM1 expression and weakened ID1's inhibition on HIF1 α ‐mediated VE‐Cad expression, thereby maintaining hepatic endothelium homeostasis. LSECs are crucial for the progression of liver steatosis into NASH, and CGA alleviated liver inflammatory injury during NASH progression by inhibiting ID1‐initiated NF κ B and HIF1 α signaling pathways through binding to TGF β R1 in LSECs. 10.1002/ptr.70095 http://onlinelibrary.wiley.com/termsAndConditions#vor |
| title | Chlorogenic Acid Alleviates Non‐Alcoholic Steatohepatitis via Suppressing Liver Inflammatory Injury by Targeting Transforming Growth Factor Beta Receptor‐1 in Liver Sinusoidal Endothelial Cells |
| topic | Phytotherapy Research |
| url | https://onlinelibrary.wiley.com/doi/10.1002/ptr.70095 |