Tags

Type your tag names separated by a space and hit enter

Sarsasapogenin restores podocyte autophagy in diabetic nephropathy by targeting GSK3β signaling pathway.
Biochem Pharmacol. 2021 10; 192:114675.BP

Abstract

Podocyte injury following abnormal podocyte autophagy plays an indispensable role in diabetic nephropathy (DN), therefore, restoration of podocyte autophagy is considered as a feasible strategy for the treatment of DN. Here, we investigated the preventive effects of sarsasapogenin (Sar), the main active ingredient in Anemarrhena asphodeloides Bunge, on the podocyte injury in diabetic rats, and tried to illustrate the mechanisms underlying the effects in high glucose (HG, 40 mM)-treated podocytes (MPs). Diabetes model was established in rats with single streptozocin (60 mg· kg-1) intraperitoneal administration. The rats were then treated with Sar (20, 60 mg· kg-1· d-1, i.g.) or a positive control drug insulin (INS) (40 U· kg-1· d-1, i.h.) for 10 weeks. Our results showed that both Sar and insulin precluded the decreases of autophagy-related proteins (ATG5, Beclin1 and LC3B) and podocyte marker proteins (podocin, nephrin and synaptopodin) in the diabetic kidney. Furthermore, network pharmacology was utilized to assess GSK3β as the potential target involved in the action of Sar on DN and were substantiated by significant changes of GSK3β signaling in the diabetic kidney. The underlying protection mechanisms of Sar were explored in HG-treated MPs. Sar (20, 40 μM) or insulin (50 mU/L) significantly increased the expression of autophagy- related proteins and podocyte marker proteins in HG-treated MPs. Furthermore, Sar or insulin treatment efficiently regulatedphosphorylation at activation and inhibition sites of GSK3β. To sum up, this study certifies that Sar meliorates experimental DN through targeting GSK3β signaling pathway and restoring podocyte autophagy.

Authors+Show Affiliations

Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, Xuzhou Medical University, 209 Tongshan Road, Xuzhou 221004, Jiangsu, China.Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, Xuzhou Medical University, 209 Tongshan Road, Xuzhou 221004, Jiangsu, China.Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, Xuzhou Medical University, 209 Tongshan Road, Xuzhou 221004, Jiangsu, China.Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, Xuzhou Medical University, 209 Tongshan Road, Xuzhou 221004, Jiangsu, China.School of Medical Information and Engineering, Xuzhou Medical University, 209 Tongshan Road, Xuzhou 221004, Jiangsu, China.Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, Xuzhou Medical University, 209 Tongshan Road, Xuzhou 221004, Jiangsu, China.Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, Xuzhou Medical University, 209 Tongshan Road, Xuzhou 221004, Jiangsu, China.Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, Xuzhou Medical University, 209 Tongshan Road, Xuzhou 221004, Jiangsu, China.Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, Xuzhou Medical University, 209 Tongshan Road, Xuzhou 221004, Jiangsu, China.Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, Xuzhou Medical University, 209 Tongshan Road, Xuzhou 221004, Jiangsu, China.Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, Xuzhou Medical University, 209 Tongshan Road, Xuzhou 221004, Jiangsu, China.Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, Xuzhou Medical University, 209 Tongshan Road, Xuzhou 221004, Jiangsu, China. Electronic address: ywliu@xzhmu.edu.cn.Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, Xuzhou Medical University, 209 Tongshan Road, Xuzhou 221004, Jiangsu, China. Electronic address: yinxx@xzhmu.edu.cn.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

34252407

Citation

Li, Xi-Zhi, et al. "Sarsasapogenin Restores Podocyte Autophagy in Diabetic Nephropathy By Targeting GSK3β Signaling Pathway." Biochemical Pharmacology, vol. 192, 2021, p. 114675.
Li XZ, Jiang H, Xu L, et al. Sarsasapogenin restores podocyte autophagy in diabetic nephropathy by targeting GSK3β signaling pathway. Biochem Pharmacol. 2021;192:114675.
Li, X. Z., Jiang, H., Xu, L., Liu, Y. Q., Tang, J. W., Shi, J. S., Yu, X. J., Wang, X., Du, L., Lu, Q., Li, C. L., Liu, Y. W., & Yin, X. X. (2021). Sarsasapogenin restores podocyte autophagy in diabetic nephropathy by targeting GSK3β signaling pathway. Biochemical Pharmacology, 192, 114675. https://doi.org/10.1016/j.bcp.2021.114675
Li XZ, et al. Sarsasapogenin Restores Podocyte Autophagy in Diabetic Nephropathy By Targeting GSK3β Signaling Pathway. Biochem Pharmacol. 2021;192:114675. PubMed PMID: 34252407.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Sarsasapogenin restores podocyte autophagy in diabetic nephropathy by targeting GSK3β signaling pathway. AU - Li,Xi-Zhi, AU - Jiang,Hong, AU - Xu,Liu, AU - Liu,Yi-Qi, AU - Tang,Jia-Wei, AU - Shi,Jia-Sen, AU - Yu,Xiu-Juan, AU - Wang,Xue, AU - Du,Lei, AU - Lu,Qian, AU - Li,Cheng-Lin, AU - Liu,Yao-Wu, AU - Yin,Xiao-Xing, Y1 - 2021/07/09/ PY - 2021/04/20/received PY - 2021/07/02/revised PY - 2021/07/06/accepted PY - 2021/7/13/pubmed PY - 2021/11/17/medline PY - 2021/7/12/entrez KW - Diabetic nephropathy KW - GSK3β KW - Network pharmacology KW - Podocyte autophagy KW - Podocyte injury KW - Sarsasapogenin SP - 114675 EP - 114675 JF - Biochemical pharmacology JO - Biochem Pharmacol VL - 192 N2 - Podocyte injury following abnormal podocyte autophagy plays an indispensable role in diabetic nephropathy (DN), therefore, restoration of podocyte autophagy is considered as a feasible strategy for the treatment of DN. Here, we investigated the preventive effects of sarsasapogenin (Sar), the main active ingredient in Anemarrhena asphodeloides Bunge, on the podocyte injury in diabetic rats, and tried to illustrate the mechanisms underlying the effects in high glucose (HG, 40 mM)-treated podocytes (MPs). Diabetes model was established in rats with single streptozocin (60 mg· kg-1) intraperitoneal administration. The rats were then treated with Sar (20, 60 mg· kg-1· d-1, i.g.) or a positive control drug insulin (INS) (40 U· kg-1· d-1, i.h.) for 10 weeks. Our results showed that both Sar and insulin precluded the decreases of autophagy-related proteins (ATG5, Beclin1 and LC3B) and podocyte marker proteins (podocin, nephrin and synaptopodin) in the diabetic kidney. Furthermore, network pharmacology was utilized to assess GSK3β as the potential target involved in the action of Sar on DN and were substantiated by significant changes of GSK3β signaling in the diabetic kidney. The underlying protection mechanisms of Sar were explored in HG-treated MPs. Sar (20, 40 μM) or insulin (50 mU/L) significantly increased the expression of autophagy- related proteins and podocyte marker proteins in HG-treated MPs. Furthermore, Sar or insulin treatment efficiently regulatedphosphorylation at activation and inhibition sites of GSK3β. To sum up, this study certifies that Sar meliorates experimental DN through targeting GSK3β signaling pathway and restoring podocyte autophagy. SN - 1873-2968 UR - https://www.unboundmedicine.com/medline/citation/34252407/Sarsasapogenin_restores_podocyte_autophagy_in_diabetic_nephropathy_by_targeting_GSK3β_signaling_pathway_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0006-2952(21)00288-4 DB - PRIME DP - Unbound Medicine ER -