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Emodin improves renal fibrosis in chronic kidney disease by regulating mitochondrial homeostasis through the mediation of peroxisome proliferator-activated receptor-gamma coactivator-1 alpha (PGC-1α)

Authors

Liuchang Feng
Department of Nephrology, Shenzhen Hospital, Beijing University of Chinese Medicine, Shenzhen, China.
Zaoqiang Lin
Department of Nephrology, Shenzhen Hospital, Beijing University of Chinese Medicine, Shenzhen, China.
Zeyong Tang
Department of Nephrology, Guangzhou University of Chinese Medicine, Guangzhou, China.
Lin Zhu
Department of Nephrology, Shenzhen Hospital; Department of Nephrology, Dongzhimen Hospital, Beijing University of Chinese Medicine, Shenzhen, China.
Shu Xu
https://orcid.org/0009-0000-3276-7407
Department of Oncology, Shenzhen Hospital, University of Chinese Academy of Sciences, Shenzhen, China.
Xi Tan
Medicopsychology, Shenzhen Hospital, Beijing University of Chinese Medicine, Shenzhen, China.
Xinyuan Wang
Medicopsychology, School of Life Sciences, Beijing University of Chinese Medicine, Beijing, China.
Jianling Mai
Department of Hemodialysis, Guangdong Provincial Hospital of Chinese Medicine, Guangzhou, China.
Qinxiang Tan
qinxiangtan2023@163.com
Department of Nephrology, Shenzhen Hospital, Beijing University of Chinese Medicine, Shenzhen, China.

Chronic kidney disease (CKD) is a leading public health issue associated with high morbidity worldwide. However, there are only a few effective therapeutic strategies for CKD. Emodin, an anthraquinone compound from rhubarb, can inhibit fibrosis in tissues and cells. Our study aims to investigate the antifibrotic effect of emodin and the underlying molecular mechanism. A unilateral ureteral obstruction (UUO)-induced rat model was established to evaluate the effect of emodin on renal fibrosis development. Hematoxylin and eosin staining, Masson’s trichrome staining, and immunohistochemistry staining were performed to analyze histopathological changes and fibrotic features after emodin treatment. Subsequently, a transforming growth factor-beta 1 (TGF-β1)-induced cell model was used to assess the inhibition of emodin on cell fibrosis in vitro. Furthermore, Western blot analysis and real-time quantitative reverse transcription-polymerase chain reaction were performed to validate the regulatory mechanism of emodin on renal fibrosis progression. As a result, emodin significantly improved histopathological abnormalities in rats with UUO. The expression of fibrosis biomarkers and mitochondrial biogenesis-related proteins also decreased after emodin treatment. Moreover, emodin blocked TGF-β1-induced fibrotic phenotype, lipid accumulation, and mitochondrial homeostasis in NRK-52E cells. Conversely, peroxisome proliferator-activated receptor-gamma coactivator-1 alpha (PGC-1α) silencing significantly reversed these features in emodin-treated cells. Collectively, emodin plays an important role in regulating PGC-1α-mediated mitochondria function and energy homeostasis. This indicates that emodin exhibits great inhibition against renal fibrosis and acts as a promising inhibitor of CKD.

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Ethics Approval

The animal experiments were conducted with protocols approved by the Experimental Animal Ethics Committee of Shenzhen Hospital of Beijing University of Traditional Chinese Medicine

Supporting Agencies

Shenzhen Hospital of Beijing University of Traditional Chinese Medicine

How to Cite

Feng, L., Lin, Z., Tang, Z., Zhu, L., Xu, S., Tan, X., … Tan, Q. (2024). Emodin improves renal fibrosis in chronic kidney disease by regulating mitochondrial homeostasis through the mediation of peroxisome proliferator-activated receptor-gamma coactivator-1 alpha (PGC-1α). European Journal of Histochemistry, 68(2). https://doi.org/10.4081/ejh.2024.3917
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