Emodin Inhibits AIM2 Inflammasome Activation via Modulating K27 ‐Linked Polyubiquitination to Attenuate Renal Fibrosis
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Wiley
2024
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| _version_ | 1867013596754477056 |
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| author | Lidan Lu Ruonan Shuang Fang Cao Zhongwen Sun Qingxue Wei Tiantian Gao Xuejing Gu Kejian Wen Xiaolan Cheng Mingjia Gu |
| author_facet | Lidan Lu Ruonan Shuang Fang Cao Zhongwen Sun Qingxue Wei Tiantian Gao Xuejing Gu Kejian Wen Xiaolan Cheng Mingjia Gu Lidan Lu Ruonan Shuang Fang Cao Zhongwen Sun Qingxue Wei Tiantian Gao Xuejing Gu Kejian Wen Xiaolan Cheng Mingjia Gu |
| collection | Wiley Open Access |
| contents | Emodin Inhibits AIM2 Inflammasome Activation via Modulating K27 ‐Linked Polyubiquitination to Attenuate Renal Fibrosis Lidan Lu Ruonan Shuang Fang Cao Zhongwen Sun Qingxue Wei Tiantian Gao Xuejing Gu Kejian Wen Xiaolan Cheng Mingjia Gu Phytotherapy Research ABSTRACT Chronic kidney diseases (CKD) is a serious threat to people's health with renal fibrosis as the major pathological feature. The absent in melanoma 2 (AIM2) has recently been proposed to play a critical role in CKD. Emodin is a major bioactive compound from rhubarb, which is widely used for clinical treatment of renal disease. The aim of this study is to elucidate the effect of emodin on unilateral ureteral obstruction (UUO) model mice and its association with the AIM2 inflammasome. In this study, we established the UUO‐induced mice renal interstitial fibrosis in vivo and bone marrow‐derived macrophages (BMDMs) model in vitro. The BUN, SCr, TNF‐α, IL‐1β in serum were examined. The degree of renal damage and fibrosis were determined by histological assessment. Immunofluorescence, western blot, and Co‐IP were used to determine the mechanisms of emodin against CKD. Emodin could improve UUO‐induced abnormal renal function and histopathological abnormalities. It could also ameliorate renal fibrosis, evidenced by inhibiting the expression of α‐SMA, TGF‐β1, FN, and collagen I. Mechanistically, emodin significantly suppressed AIM2 inflammasome as well as its components including ASC, cleaved caspase‐1, and IL‐1β both in vivo and in vitro. Further studies demonstrated that emodin inhibited K27‐linked polyubiquitination of AIM2 by targeting on K64 sites of the lysine residues. In summary, emodin could hinder the activation of AIM2 inflammasome in UUO model mice through K27‐linked polyubiquitination to reduce renal fibrosis. Emodin is a possible therapeutic option for CKD treatment. 10.1002/ptr.8390 http://onlinelibrary.wiley.com/termsAndConditions#vor |
| doi_str_mv | 10.1002/ptr.8390 |
| format | Artículo Open Access |
| id | wiley_oa_10_1002_ptr_8390 |
| institution | Wiley Open Access |
| license_str_mv | http://onlinelibrary.wiley.com/termsAndConditions#vor |
| publishDate | 2024 |
| publisher | Wiley |
| record_format | wiley_oa |
| spellingShingle | Emodin Inhibits AIM2 Inflammasome Activation via Modulating K27 ‐Linked Polyubiquitination to Attenuate Renal Fibrosis Lidan Lu Ruonan Shuang Fang Cao Zhongwen Sun Qingxue Wei Tiantian Gao Xuejing Gu Kejian Wen Xiaolan Cheng Mingjia Gu Phytotherapy Research Emodin Inhibits AIM2 Inflammasome Activation via Modulating K27 ‐Linked Polyubiquitination to Attenuate Renal Fibrosis Lidan Lu Ruonan Shuang Fang Cao Zhongwen Sun Qingxue Wei Tiantian Gao Xuejing Gu Kejian Wen Xiaolan Cheng Mingjia Gu Phytotherapy Research ABSTRACT Chronic kidney diseases (CKD) is a serious threat to people's health with renal fibrosis as the major pathological feature. The absent in melanoma 2 (AIM2) has recently been proposed to play a critical role in CKD. Emodin is a major bioactive compound from rhubarb, which is widely used for clinical treatment of renal disease. The aim of this study is to elucidate the effect of emodin on unilateral ureteral obstruction (UUO) model mice and its association with the AIM2 inflammasome. In this study, we established the UUO‐induced mice renal interstitial fibrosis in vivo and bone marrow‐derived macrophages (BMDMs) model in vitro. The BUN, SCr, TNF‐α, IL‐1β in serum were examined. The degree of renal damage and fibrosis were determined by histological assessment. Immunofluorescence, western blot, and Co‐IP were used to determine the mechanisms of emodin against CKD. Emodin could improve UUO‐induced abnormal renal function and histopathological abnormalities. It could also ameliorate renal fibrosis, evidenced by inhibiting the expression of α‐SMA, TGF‐β1, FN, and collagen I. Mechanistically, emodin significantly suppressed AIM2 inflammasome as well as its components including ASC, cleaved caspase‐1, and IL‐1β both in vivo and in vitro. Further studies demonstrated that emodin inhibited K27‐linked polyubiquitination of AIM2 by targeting on K64 sites of the lysine residues. In summary, emodin could hinder the activation of AIM2 inflammasome in UUO model mice through K27‐linked polyubiquitination to reduce renal fibrosis. Emodin is a possible therapeutic option for CKD treatment. 10.1002/ptr.8390 http://onlinelibrary.wiley.com/termsAndConditions#vor |
| title | Emodin Inhibits AIM2 Inflammasome Activation via Modulating K27 ‐Linked Polyubiquitination to Attenuate Renal Fibrosis |
| topic | Phytotherapy Research |
| url | https://onlinelibrary.wiley.com/doi/10.1002/ptr.8390 |