Protective Role of Tangshen Formula on the Progression of Renal Damage in db/db Mice by TRPC6/Talin1 Pathway in Podocytes
Tangshen Formula (TSF) is a Chinese Medicine formula that has been reported to alleviate proteinuria and protect renal function in humans and animals with diabetic kidney disease (DKD). However, little is known about its mechanism in improving proteinuria. The dysregulation of podocyte cell-matrix a...
Saved in:
| Main Authors: | , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Wiley
2020-01-01
|
| Series: | Journal of Diabetes Research |
| Online Access: | http://dx.doi.org/10.1155/2020/3634974 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1850174393021366272 |
|---|---|
| author | Qian Wang Xuefei Tian Wei’e Zhou Yan Wang Hailing Zhao Jialin Li Xuefeng Zhou Haojun Zhang Tingting Zhao Ping Li |
| author_facet | Qian Wang Xuefei Tian Wei’e Zhou Yan Wang Hailing Zhao Jialin Li Xuefeng Zhou Haojun Zhang Tingting Zhao Ping Li |
| author_sort | Qian Wang |
| collection | DOAJ |
| description | Tangshen Formula (TSF) is a Chinese Medicine formula that has been reported to alleviate proteinuria and protect renal function in humans and animals with diabetic kidney disease (DKD). However, little is known about its mechanism in improving proteinuria. The dysregulation of podocyte cell-matrix adhesion has been demonstrated to play an important role in the pathogenesis and progression of proteinuric kidney diseases including DKD. In the present study, the underlying protective mechanism of TSF on podocytes was investigated using the murine model of type 2 DKD db/db mice in vivo and advanced glycation end products (AGEs)-stimulated primary mice podocytes in vitro. Results revealed that TSF treatment could significantly mitigate reduction of podocyte numbers and foot process effacement, reduce proteinuria, and protect renal function in db/db mice. There was a significant increase in expression of transient receptor potential canonical channel 6 (TRPC6) and a decrease in expression of talin1 in podocytes of db/db mice. The results of AGEs-stimulated primary mice podocytes showed increased cell migration and actin-cytoskeleton rearrangement. Moreover, primary mice podocytes stimulated by AGEs displayed an increase in TRPC6-dependent Ca2+ influx, a loss of talin1, and translocation of nuclear factor of activated T cell (NFATC) 2. These dysregulations in mice primary podocytes stimulated by AGEs could be significantly attenuated after TSF treatment. 1-Oleoyl-2-acetyl-sn-glycerol (OAG), a TRPC6 agonist, blocked the protective role of TSF on podocyte cell-matrix adherence. In conclusion, TSF could protect podocytes from injury and reduce proteinuria in DKD, which may be mediated by the regulation of the TRPC6/Talin1 pathway in podocytes. |
| format | Article |
| id | doaj-art-c8be141d189449c082e92037f02c729e |
| institution | OA Journals |
| issn | 2314-6745 2314-6753 |
| language | English |
| publishDate | 2020-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Journal of Diabetes Research |
| spelling | doaj-art-c8be141d189449c082e92037f02c729e2025-08-20T02:19:40ZengWileyJournal of Diabetes Research2314-67452314-67532020-01-01202010.1155/2020/36349743634974Protective Role of Tangshen Formula on the Progression of Renal Damage in db/db Mice by TRPC6/Talin1 Pathway in PodocytesQian Wang0Xuefei Tian1Wei’e Zhou2Yan Wang3Hailing Zhao4Jialin Li5Xuefeng Zhou6Haojun Zhang7Tingting Zhao8Ping Li9Beijing University of Chinese Medicine, Beijing 100029, ChinaSection of Nephrology, Department of Internal Medicine, Yale University School of Medicine, New Haven, CT 06510, USABeijing Key Laboratory for Immune-Mediated Inflammatory Diseases, Institute of Clinical Medical Sciences, China-Japan Friendship Hospital, Beijing 100029, ChinaBeijing Key Laboratory of Diabetes Research and Care, Center for Endocrine Metabolism and Immune Diseases, Lu He Hospital, Capital Medical University, Beijing 101149, ChinaBeijing Key Laboratory for Immune-Mediated Inflammatory Diseases, Institute of Clinical Medical Sciences, China-Japan Friendship Hospital, Beijing 100029, ChinaBeijing University of Chinese Medicine, Beijing 100029, ChinaBeijing University of Chinese Medicine, Beijing 100029, ChinaBeijing Key Laboratory for Immune-Mediated Inflammatory Diseases, Institute of Clinical Medical Sciences, China-Japan Friendship Hospital, Beijing 100029, ChinaBeijing Key Laboratory for Immune-Mediated Inflammatory Diseases, Institute of Clinical Medical Sciences, China-Japan Friendship Hospital, Beijing 100029, ChinaBeijing Key Laboratory for Immune-Mediated Inflammatory Diseases, Institute of Clinical Medical Sciences, China-Japan Friendship Hospital, Beijing 100029, ChinaTangshen Formula (TSF) is a Chinese Medicine formula that has been reported to alleviate proteinuria and protect renal function in humans and animals with diabetic kidney disease (DKD). However, little is known about its mechanism in improving proteinuria. The dysregulation of podocyte cell-matrix adhesion has been demonstrated to play an important role in the pathogenesis and progression of proteinuric kidney diseases including DKD. In the present study, the underlying protective mechanism of TSF on podocytes was investigated using the murine model of type 2 DKD db/db mice in vivo and advanced glycation end products (AGEs)-stimulated primary mice podocytes in vitro. Results revealed that TSF treatment could significantly mitigate reduction of podocyte numbers and foot process effacement, reduce proteinuria, and protect renal function in db/db mice. There was a significant increase in expression of transient receptor potential canonical channel 6 (TRPC6) and a decrease in expression of talin1 in podocytes of db/db mice. The results of AGEs-stimulated primary mice podocytes showed increased cell migration and actin-cytoskeleton rearrangement. Moreover, primary mice podocytes stimulated by AGEs displayed an increase in TRPC6-dependent Ca2+ influx, a loss of talin1, and translocation of nuclear factor of activated T cell (NFATC) 2. These dysregulations in mice primary podocytes stimulated by AGEs could be significantly attenuated after TSF treatment. 1-Oleoyl-2-acetyl-sn-glycerol (OAG), a TRPC6 agonist, blocked the protective role of TSF on podocyte cell-matrix adherence. In conclusion, TSF could protect podocytes from injury and reduce proteinuria in DKD, which may be mediated by the regulation of the TRPC6/Talin1 pathway in podocytes.http://dx.doi.org/10.1155/2020/3634974 |
| spellingShingle | Qian Wang Xuefei Tian Wei’e Zhou Yan Wang Hailing Zhao Jialin Li Xuefeng Zhou Haojun Zhang Tingting Zhao Ping Li Protective Role of Tangshen Formula on the Progression of Renal Damage in db/db Mice by TRPC6/Talin1 Pathway in Podocytes Journal of Diabetes Research |
| title | Protective Role of Tangshen Formula on the Progression of Renal Damage in db/db Mice by TRPC6/Talin1 Pathway in Podocytes |
| title_full | Protective Role of Tangshen Formula on the Progression of Renal Damage in db/db Mice by TRPC6/Talin1 Pathway in Podocytes |
| title_fullStr | Protective Role of Tangshen Formula on the Progression of Renal Damage in db/db Mice by TRPC6/Talin1 Pathway in Podocytes |
| title_full_unstemmed | Protective Role of Tangshen Formula on the Progression of Renal Damage in db/db Mice by TRPC6/Talin1 Pathway in Podocytes |
| title_short | Protective Role of Tangshen Formula on the Progression of Renal Damage in db/db Mice by TRPC6/Talin1 Pathway in Podocytes |
| title_sort | protective role of tangshen formula on the progression of renal damage in db db mice by trpc6 talin1 pathway in podocytes |
| url | http://dx.doi.org/10.1155/2020/3634974 |
| work_keys_str_mv | AT qianwang protectiveroleoftangshenformulaontheprogressionofrenaldamageindbdbmicebytrpc6talin1pathwayinpodocytes AT xuefeitian protectiveroleoftangshenformulaontheprogressionofrenaldamageindbdbmicebytrpc6talin1pathwayinpodocytes AT weiezhou protectiveroleoftangshenformulaontheprogressionofrenaldamageindbdbmicebytrpc6talin1pathwayinpodocytes AT yanwang protectiveroleoftangshenformulaontheprogressionofrenaldamageindbdbmicebytrpc6talin1pathwayinpodocytes AT hailingzhao protectiveroleoftangshenformulaontheprogressionofrenaldamageindbdbmicebytrpc6talin1pathwayinpodocytes AT jialinli protectiveroleoftangshenformulaontheprogressionofrenaldamageindbdbmicebytrpc6talin1pathwayinpodocytes AT xuefengzhou protectiveroleoftangshenformulaontheprogressionofrenaldamageindbdbmicebytrpc6talin1pathwayinpodocytes AT haojunzhang protectiveroleoftangshenformulaontheprogressionofrenaldamageindbdbmicebytrpc6talin1pathwayinpodocytes AT tingtingzhao protectiveroleoftangshenformulaontheprogressionofrenaldamageindbdbmicebytrpc6talin1pathwayinpodocytes AT pingli protectiveroleoftangshenformulaontheprogressionofrenaldamageindbdbmicebytrpc6talin1pathwayinpodocytes |