Emodin Ameliorates Renal Damage and Podocyte Injury in a Rat Model of Diabetic Nephropathy via Regulating AMPK/mTOR-Mediated Autophagy Signaling Pathway
Hong Liu,1,* Quan Wang,1,* Ge Shi,1 Wenqiang Yang,2 Yanmin Zhang,1 Weidong Chen,1 Sheng Wan,1 Fei Xiong,1 Zengsi Wang1 1Department of Nephrology, Wuhan No. 1 Hospital, Wuhan, Hubei, 430022, People’s Republic of China; 2Department of Central Laboratory, Wuhan No. 1 Hospital, Wuhan, Hubei, 4...
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Dove Medical Press
2021
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oai:doaj.org-article:2fcb13e8b0e947d783780a12720377f02021-12-02T11:39:16ZEmodin Ameliorates Renal Damage and Podocyte Injury in a Rat Model of Diabetic Nephropathy via Regulating AMPK/mTOR-Mediated Autophagy Signaling Pathway1178-7007https://doaj.org/article/2fcb13e8b0e947d783780a12720377f02021-03-01T00:00:00Zhttps://www.dovepress.com/emodin-ameliorates-renal-damage-and-podocyte-injury-in-a-rat-model-of--peer-reviewed-article-DMSOhttps://doaj.org/toc/1178-7007Hong Liu,1,* Quan Wang,1,* Ge Shi,1 Wenqiang Yang,2 Yanmin Zhang,1 Weidong Chen,1 Sheng Wan,1 Fei Xiong,1 Zengsi Wang1 1Department of Nephrology, Wuhan No. 1 Hospital, Wuhan, Hubei, 430022, People’s Republic of China; 2Department of Central Laboratory, Wuhan No. 1 Hospital, Wuhan, Hubei, 430022, People’s Republic of China*These authors contributed equally to this workCorrespondence: Fei Xiong; Zengsi WangDepartment of Nephrology, Wuhan No. 1 Hospital, No. 215 Zhongshan Avenue, Wuhan, Hubei, 430022, People’s Republic of ChinaTel +86-27-85332356; +86-27-85332346Email xiongf23@sina.com; wangzengsi@hotmail.comPurpose: The activation of autophagy has potential protective effect on diabetic nephropathy (DN) podocyte injury, and the AMPK/mTOR signaling pathway is an important regulatory pathway of autophagy. Emodin has been reported to effectively delay DN progression; however, the therapeutic mechanisms involved in vivo remain ambiguous. The present study aimed to elucidate the mechanism of emodin in improving renal tissue and podocyte injury in DN by regulating the AMPK/mTOR-autophagy signaling pathway.Methods: All rats were divided into 4 groups: a Sham group, a Vehicle group, a low-dose emodin (LD-Emo) group (20 mg/kg/day) and a high-dose emodin (HD-Emo) group (40 mg/kg/day). The different doses of Emo and distilled water were daily administrated for 8 weeks after the induction of DN by the unilateral nephrectomy combined with intraperitoneal injections of streptozotocin (STZ). The rats’ general status, blood glucose, biochemical parameters, urinary protein excretion, renal histological changes and cell apoptosis in renal tissue, as well as the key protein expressions in the AMPK/mTOR signaling pathway and apoptosis-related proteins were examined, respectively.Results: Emodin ameliorated the general condition, kidney weight and urinary protein excretion of the rats, but has little influence on serum biochemical parameters and did not lower blood glucose; emodin attenuated renal fibrosis including the cell numbers, extracellular matrix rate and collagen area in glomerulus, simultaneously relieved podocyte foot process fusion, up-regulated the expression of nephrin protein and suppressed glomerular and tubular epithelial cell apoptosis. In addition, emodin can induce and enhance autophagy in podocytes including increased expression of LC3-II/I, Beclin-1, p-AMPK protein and decreased expression of p62, p-mTOR protein, as well as increased autophagosomes in podocytes.Conclusion: We have demonstrated that emodin, as a natural regulator in vivo, reduced proteinuria and alleviated renal fibrosis without affecting hyperglycemia in DN rats. The potential mechanisms by which emodin exerts its renoprotective effects in vivo are through suppressing cell apoptosis and enhancing autophagy of podocytes via the AMPK/mTOR signaling pathway in the kidney.Keywords: emodin, diabetic nephropathy, autophagy, cell apoptosis, AMPK/mTOR signaling pathwayLiu HWang QShi GYang WZhang YChen WWan SXiong FWang ZDove Medical Pressarticleemodindiabetic nephropathyautophagycell apoptosisampk/mtor signaling pathwaySpecialties of internal medicineRC581-951ENDiabetes, Metabolic Syndrome and Obesity: Targets and Therapy, Vol Volume 14, Pp 1253-1266 (2021) |
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DOAJ |
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EN |
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emodin diabetic nephropathy autophagy cell apoptosis ampk/mtor signaling pathway Specialties of internal medicine RC581-951 |
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emodin diabetic nephropathy autophagy cell apoptosis ampk/mtor signaling pathway Specialties of internal medicine RC581-951 Liu H Wang Q Shi G Yang W Zhang Y Chen W Wan S Xiong F Wang Z Emodin Ameliorates Renal Damage and Podocyte Injury in a Rat Model of Diabetic Nephropathy via Regulating AMPK/mTOR-Mediated Autophagy Signaling Pathway |
| description |
Hong Liu,1,* Quan Wang,1,* Ge Shi,1 Wenqiang Yang,2 Yanmin Zhang,1 Weidong Chen,1 Sheng Wan,1 Fei Xiong,1 Zengsi Wang1 1Department of Nephrology, Wuhan No. 1 Hospital, Wuhan, Hubei, 430022, People’s Republic of China; 2Department of Central Laboratory, Wuhan No. 1 Hospital, Wuhan, Hubei, 430022, People’s Republic of China*These authors contributed equally to this workCorrespondence: Fei Xiong; Zengsi WangDepartment of Nephrology, Wuhan No. 1 Hospital, No. 215 Zhongshan Avenue, Wuhan, Hubei, 430022, People’s Republic of ChinaTel +86-27-85332356; +86-27-85332346Email xiongf23@sina.com; wangzengsi@hotmail.comPurpose: The activation of autophagy has potential protective effect on diabetic nephropathy (DN) podocyte injury, and the AMPK/mTOR signaling pathway is an important regulatory pathway of autophagy. Emodin has been reported to effectively delay DN progression; however, the therapeutic mechanisms involved in vivo remain ambiguous. The present study aimed to elucidate the mechanism of emodin in improving renal tissue and podocyte injury in DN by regulating the AMPK/mTOR-autophagy signaling pathway.Methods: All rats were divided into 4 groups: a Sham group, a Vehicle group, a low-dose emodin (LD-Emo) group (20 mg/kg/day) and a high-dose emodin (HD-Emo) group (40 mg/kg/day). The different doses of Emo and distilled water were daily administrated for 8 weeks after the induction of DN by the unilateral nephrectomy combined with intraperitoneal injections of streptozotocin (STZ). The rats’ general status, blood glucose, biochemical parameters, urinary protein excretion, renal histological changes and cell apoptosis in renal tissue, as well as the key protein expressions in the AMPK/mTOR signaling pathway and apoptosis-related proteins were examined, respectively.Results: Emodin ameliorated the general condition, kidney weight and urinary protein excretion of the rats, but has little influence on serum biochemical parameters and did not lower blood glucose; emodin attenuated renal fibrosis including the cell numbers, extracellular matrix rate and collagen area in glomerulus, simultaneously relieved podocyte foot process fusion, up-regulated the expression of nephrin protein and suppressed glomerular and tubular epithelial cell apoptosis. In addition, emodin can induce and enhance autophagy in podocytes including increased expression of LC3-II/I, Beclin-1, p-AMPK protein and decreased expression of p62, p-mTOR protein, as well as increased autophagosomes in podocytes.Conclusion: We have demonstrated that emodin, as a natural regulator in vivo, reduced proteinuria and alleviated renal fibrosis without affecting hyperglycemia in DN rats. The potential mechanisms by which emodin exerts its renoprotective effects in vivo are through suppressing cell apoptosis and enhancing autophagy of podocytes via the AMPK/mTOR signaling pathway in the kidney.Keywords: emodin, diabetic nephropathy, autophagy, cell apoptosis, AMPK/mTOR signaling pathway |
| format |
article |
| author |
Liu H Wang Q Shi G Yang W Zhang Y Chen W Wan S Xiong F Wang Z |
| author_facet |
Liu H Wang Q Shi G Yang W Zhang Y Chen W Wan S Xiong F Wang Z |
| author_sort |
Liu H |
| title |
Emodin Ameliorates Renal Damage and Podocyte Injury in a Rat Model of Diabetic Nephropathy via Regulating AMPK/mTOR-Mediated Autophagy Signaling Pathway |
| title_short |
Emodin Ameliorates Renal Damage and Podocyte Injury in a Rat Model of Diabetic Nephropathy via Regulating AMPK/mTOR-Mediated Autophagy Signaling Pathway |
| title_full |
Emodin Ameliorates Renal Damage and Podocyte Injury in a Rat Model of Diabetic Nephropathy via Regulating AMPK/mTOR-Mediated Autophagy Signaling Pathway |
| title_fullStr |
Emodin Ameliorates Renal Damage and Podocyte Injury in a Rat Model of Diabetic Nephropathy via Regulating AMPK/mTOR-Mediated Autophagy Signaling Pathway |
| title_full_unstemmed |
Emodin Ameliorates Renal Damage and Podocyte Injury in a Rat Model of Diabetic Nephropathy via Regulating AMPK/mTOR-Mediated Autophagy Signaling Pathway |
| title_sort |
emodin ameliorates renal damage and podocyte injury in a rat model of diabetic nephropathy via regulating ampk/mtor-mediated autophagy signaling pathway |
| publisher |
Dove Medical Press |
| publishDate |
2021 |
| url |
https://doaj.org/article/2fcb13e8b0e947d783780a12720377f0 |
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