Tangshen Formula Attenuates Diabetic Nephropathy by Promoting ABCA1-Mediated Renal Cholesterol Efflux in db/db Mice
The commonly prescribed Tangshen Formula (TSF) is a traditional Chinese formulation that has been shown to reduce plasma lipid metabolism and proteinuria and improve the estimated glomerular filtration rate (eGFR) in patients with diabetic kidney disease. This study investigated the underlying mecha...
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Frontiers Media S.A.
2018-04-01
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| Series: | Frontiers in Physiology |
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| Online Access: | http://journal.frontiersin.org/article/10.3389/fphys.2018.00343/full |
| _version_ | 1819084565159870464 |
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| author | Peng Liu Peng Liu Peng Liu Liang Peng Haojun Zhang Patrick Ming-Kuen Tang Tingting Zhao Meihua Yan Hailing Zhao Xiaoru Huang Huiyao Lan Ping Li |
| author_facet | Peng Liu Peng Liu Peng Liu Liang Peng Haojun Zhang Patrick Ming-Kuen Tang Tingting Zhao Meihua Yan Hailing Zhao Xiaoru Huang Huiyao Lan Ping Li |
| author_sort | Peng Liu |
| collection | DOAJ |
| description | The commonly prescribed Tangshen Formula (TSF) is a traditional Chinese formulation that has been shown to reduce plasma lipid metabolism and proteinuria and improve the estimated glomerular filtration rate (eGFR) in patients with diabetic kidney disease. This study investigated the underlying mechanism whereby TSF regulates renal lipid accumulation and ameliorates diabetic renal injuries in spontaneous diabetic db/db mice and in vitro in sodium palmitate (PA)-stimulated and Abca1-SiRNA-transfected mouse tubular epithelial cells (mTECs). The results revealed that TSF treatment significantly ameliorated the renal injuries by lowering urinary albumin excretion and improving renal tissue injuries in diabetic (db/db) mice. Interestingly, the treatment with TSF also resulted in decreased cholesterol levels in the renal tissues of db/db mice, which was associated with increased expression of the peroxisome proliferator-activated receptor γ coactivator 1-α (PGC-1α), the Liver X receptors (LXR), and ATP-binding cassette subfamily A member 1 (ABCA1), suggesting that TSF might attenuate diabetic kidney injury via a mechanism associated with improving cholesterol efflux in the diabetic kidney. This was investigated in vitro in mTECs, and the results showed that TSF reduced the PA-stimulated cholesterol accumulation in mTECs. Mechanistically, the addition of TSF was capable of reversing PA-induced downregulation of PGC-1α, LXR, and ABCA1 expression and cholesterol accumulation in mTECs, suggesting that TSF might act the protection via the PGC-1α-LXR-ABCA1 pathway to improve the cholesterol efflux in the renal tissues of db/db mice. This was further confirmed by silencing ABCA1 to block the promotive effect of TSF on cholesterol efflux in vitro. In conclusion, TSF might ameliorate diabetic kidney injuries by promoting ABCA1-mediated renal cholesterol efflux. |
| first_indexed | 2024-12-21T20:50:29Z |
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| id | doaj.art-f7963645d1234396a7134b0693ec4fee |
| institution | Directory Open Access Journal |
| issn | 1664-042X |
| language | English |
| last_indexed | 2024-12-21T20:50:29Z |
| publishDate | 2018-04-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Physiology |
| spelling | doaj.art-f7963645d1234396a7134b0693ec4fee2022-12-21T18:50:44ZengFrontiers Media S.A.Frontiers in Physiology1664-042X2018-04-01910.3389/fphys.2018.00343340129Tangshen Formula Attenuates Diabetic Nephropathy by Promoting ABCA1-Mediated Renal Cholesterol Efflux in db/db MicePeng Liu0Peng Liu1Peng Liu2Liang Peng3Haojun Zhang4Patrick Ming-Kuen Tang5Tingting Zhao6Meihua Yan7Hailing Zhao8Xiaoru Huang9Huiyao Lan10Ping Li11Beijing Key Lab Immune-Mediated Inflammatory Diseases, Institute of Clinical Medical Sciences, China-Japan Friendship Hospital, Beijing, ChinaGraduate School of Peking Union Medical College, Chinese Academy of Medical Science & Peking Union Medical College, Beijing, ChinaLi Ka Shing Institute of Health Sciences and Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong, Hong KongBeijing Key Lab Immune-Mediated Inflammatory Diseases, Institute of Clinical Medical Sciences, China-Japan Friendship Hospital, Beijing, ChinaBeijing Key Lab Immune-Mediated Inflammatory Diseases, Institute of Clinical Medical Sciences, China-Japan Friendship Hospital, Beijing, ChinaDepartment of Anatomical and Cellular Pathology, The Chinese University of Hong Kong, Hong Kong, Hong KongBeijing Key Lab Immune-Mediated Inflammatory Diseases, Institute of Clinical Medical Sciences, China-Japan Friendship Hospital, Beijing, ChinaBeijing Key Lab Immune-Mediated Inflammatory Diseases, Institute of Clinical Medical Sciences, China-Japan Friendship Hospital, Beijing, ChinaBeijing Key Lab Immune-Mediated Inflammatory Diseases, Institute of Clinical Medical Sciences, China-Japan Friendship Hospital, Beijing, ChinaLi Ka Shing Institute of Health Sciences and Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong, Hong KongLi Ka Shing Institute of Health Sciences and Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong, Hong KongBeijing Key Lab Immune-Mediated Inflammatory Diseases, Institute of Clinical Medical Sciences, China-Japan Friendship Hospital, Beijing, ChinaThe commonly prescribed Tangshen Formula (TSF) is a traditional Chinese formulation that has been shown to reduce plasma lipid metabolism and proteinuria and improve the estimated glomerular filtration rate (eGFR) in patients with diabetic kidney disease. This study investigated the underlying mechanism whereby TSF regulates renal lipid accumulation and ameliorates diabetic renal injuries in spontaneous diabetic db/db mice and in vitro in sodium palmitate (PA)-stimulated and Abca1-SiRNA-transfected mouse tubular epithelial cells (mTECs). The results revealed that TSF treatment significantly ameliorated the renal injuries by lowering urinary albumin excretion and improving renal tissue injuries in diabetic (db/db) mice. Interestingly, the treatment with TSF also resulted in decreased cholesterol levels in the renal tissues of db/db mice, which was associated with increased expression of the peroxisome proliferator-activated receptor γ coactivator 1-α (PGC-1α), the Liver X receptors (LXR), and ATP-binding cassette subfamily A member 1 (ABCA1), suggesting that TSF might attenuate diabetic kidney injury via a mechanism associated with improving cholesterol efflux in the diabetic kidney. This was investigated in vitro in mTECs, and the results showed that TSF reduced the PA-stimulated cholesterol accumulation in mTECs. Mechanistically, the addition of TSF was capable of reversing PA-induced downregulation of PGC-1α, LXR, and ABCA1 expression and cholesterol accumulation in mTECs, suggesting that TSF might act the protection via the PGC-1α-LXR-ABCA1 pathway to improve the cholesterol efflux in the renal tissues of db/db mice. This was further confirmed by silencing ABCA1 to block the promotive effect of TSF on cholesterol efflux in vitro. In conclusion, TSF might ameliorate diabetic kidney injuries by promoting ABCA1-mediated renal cholesterol efflux.http://journal.frontiersin.org/article/10.3389/fphys.2018.00343/fullTangshen formula (TSF)diabetic nephropathy (DN)renal cholesterol effluxABCA1Abca1-SiRNA |
| spellingShingle | Peng Liu Peng Liu Peng Liu Liang Peng Haojun Zhang Patrick Ming-Kuen Tang Tingting Zhao Meihua Yan Hailing Zhao Xiaoru Huang Huiyao Lan Ping Li Tangshen Formula Attenuates Diabetic Nephropathy by Promoting ABCA1-Mediated Renal Cholesterol Efflux in db/db Mice Frontiers in Physiology Tangshen formula (TSF) diabetic nephropathy (DN) renal cholesterol efflux ABCA1 Abca1-SiRNA |
| title | Tangshen Formula Attenuates Diabetic Nephropathy by Promoting ABCA1-Mediated Renal Cholesterol Efflux in db/db Mice |
| title_full | Tangshen Formula Attenuates Diabetic Nephropathy by Promoting ABCA1-Mediated Renal Cholesterol Efflux in db/db Mice |
| title_fullStr | Tangshen Formula Attenuates Diabetic Nephropathy by Promoting ABCA1-Mediated Renal Cholesterol Efflux in db/db Mice |
| title_full_unstemmed | Tangshen Formula Attenuates Diabetic Nephropathy by Promoting ABCA1-Mediated Renal Cholesterol Efflux in db/db Mice |
| title_short | Tangshen Formula Attenuates Diabetic Nephropathy by Promoting ABCA1-Mediated Renal Cholesterol Efflux in db/db Mice |
| title_sort | tangshen formula attenuates diabetic nephropathy by promoting abca1 mediated renal cholesterol efflux in db db mice |
| topic | Tangshen formula (TSF) diabetic nephropathy (DN) renal cholesterol efflux ABCA1 Abca1-SiRNA |
| url | http://journal.frontiersin.org/article/10.3389/fphys.2018.00343/full |
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