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2000
Volume 25, Issue 7
  • ISSN: 1566-5240
  • E-ISSN: 1875-5666

Abstract

Background

Podocyte injury is the most important pathological hallmark of kidney diseases. Autophagy is a critical factor that involves podocyte injury. Here, we sought to determine whether Astragaloside IV (AS-IV) was able to improve renal function and reverse podocyte injury through the regulation of autophagy.

Methods

Using the Adriamycin (ADR) mice model, cultured immortalized mouse podocytes were exposed to AS-IV. Western blotting, immunofluorescence, and histochemistry were used to analyze markers of autophagy, mitochondrial dysfunction, podocyte apoptosis, and glomerulopathy in the progression of focal segmental glomerular sclerosis.

Results

We observed that AS-IV can inhibit podocyte apoptosis, increased reactive oxygen species (ROS) generation, mitochondrial fragmentation, and dysfunction by inducing the Mfn2/Pink1/Parkin mitophagy pathway both and . Over-expression of Mfn2 reduced puromycin aminonucleoside (PAN)-induced podocyte injury, while downregulation of Mfn2 expression limited the renal protective effect of AS-IV by regulating mitophagy.

Conclusion

AS-IV ameliorates renal function and renal pathological changes in ADR mice and inhibits PAN-induced podocyte injury by directly enhancing Mfn2/Pink1/Parkin-associated autophagy.

© 2025 Bentham Science Publishers
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2024-06-11
2025-10-27

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References

  1. KoppJ.B. AndersH.J. SusztakK. Podocytopathies.Nat. Rev. Dis. Primers2020616810.1038/s41572‑020‑0196‑7 32792490
     [Google Scholar]
  2. LiuM. LiangK. ZhenJ. Sirt6 deficiency exacerbates podocyte injury and proteinuria through targeting Notch signaling.Nat. Commun.20178141310.1038/s41467‑017‑00498‑4 28871079
     [Google Scholar]
  3. PavenstädtH. KrizW. KretzlerM. Cell biology of the glomerular podocyte.Physiol. Rev.200383125330710.1152/physrev.00020.2002 12506131
     [Google Scholar]
  4. WigginsR.C. The spectrum of podocytopathies: A unifying view of glomerular diseases.Kidney Int.200771121205121410.1038/sj.ki.5002222 17410103
     [Google Scholar]
  5. XiongW. MaZ. AnD. Mitofusin 2 participates in mitophagy and mitochondrial fusion against angiotensin II-induced cardiomyocyte injury.Front. Physiol.20191041110.3389/fphys.2019.00411
     [Google Scholar]
  6. MizushimaN. LevineB. CuervoA.M. KlionskyD.J. Autophagy fights disease through cellular self-digestion.Nature200845171821069107510.1038/nature06639
     [Google Scholar]
  7. OhsumiY. Historical landmarks of autophagy research.Cell Res.201424192310.1038/cr.2013.169 24366340
     [Google Scholar]
  8. CaoY.L. MengS. ChenY. FengJ.X. GuD.D. YuB. MFN1 structures reveal nucleotide-triggered dimerization critical For mitochondrial fusion.Nature2017542764137237610.1038/nature21077
     [Google Scholar]
  9. ChenY. DornG.W.II PINK1-phosphorylated mitofusin 2 is a Parkin receptor for culling damaged mitochondria.Science2013340613147147510.1126/science.1231031 23620051
     [Google Scholar]
  10. JiangX.S. ChenX.M. HuaW. PINK1/Parkin mediated mitophagy ameliorates palmitic acid-induced apoptosis through reducing mitochondrial ROS production in podocytes.Biochem. Biophys. Res. Commun.2020525495496110.1016/j.bbrc.2020.02.170
     [Google Scholar]
  11. QuY.Z. LiM. ZhaoY.L. Astragaloside IV attenuates cerebral ischemia–reperfusion-induced increase in permeability of the blood-brain barrier in rats.Eur. J. Pharmacol.20096061-313714110.1016/j.ejphar.2009.01.022 19374856
     [Google Scholar]
  12. YeQ. SuL. ChenD. ZhengW. LiuY. AstragalosideI.V. Astragaloside IV induced miR-134 expression reduces emt and increases chemotherapeutic sensitivity by suppressing CREB1 signaling in colorectal cancer cell Line SW-480.Cell. Physiol. Biochem.20174341617162610.1159/000482025 29041002
     [Google Scholar]
  13. CaiZ. LiuJ. BianH. CaiJ. Astragaloside IV ameliorates necrotizing enterocolitis by attenuating oxidative stress and suppressing inflammation via the vitamin D3-upregulated protein 1/NF-κB signaling pathway.Exp. Ther. Med.20161242702270810.3892/etm.2016.3629 27698775
     [Google Scholar]
  14. GuoH. WangY. ZhangX. Astragaloside IV protects against podocyte injury via SERCA2-dependent ER stress reduction and AMPKα-regulated autophagy induction in streptozotocin-induced diabetic nephropathy.Sci. Rep.201771685210.1038/s41598‑017‑07061‑7 28761152
     [Google Scholar]
  15. WangX. GaoY. TianN. Astragaloside IV represses high glucose-induced mesangial cells activation by enhancing autophagy via SIRT1 deacetylation of NF-κB P65 subunit.Drug Des. Devel. Ther.2018122971298010.2147/DDDT.S174058 30254426
     [Google Scholar]
  16. BarisoniL. Podocyte biology in segmental sclerosis and progressive glomerular injury.Adv. Chronic Kidney Dis.2012192768310.1053/j.ackd.2012.02.018 22449344
     [Google Scholar]
  17. D’AgatiV.D. Podocyte injury in focal segmental glomerulosclerosis: Lessons from animal models (a play in five acts).Kidney Int.200873439940610.1038/sj.ki.5002655 17989648
     [Google Scholar]
  18. ZengC. FanY. WuJ. Podocyte autophagic activity plays a protective role in renal injury and delays the progression of podocytopathies.J. Pathol.2014234220321310.1002/path.4382 24870816
     [Google Scholar]
  19. LeeS.Y. TsaiW.C. LinJ.C. Astragaloside II promotes intestinal epithelial repair by enhancing L-arginine uptake and activating the mTOR pathway.Sci. Rep.2017711230210.1038/s41598‑017‑12435‑y 28951595
     [Google Scholar]
  20. QiY. GaoF. HouL. WanC. Anti-inflammatory and immunostimulatory activities of astragalosides.Am. J. Chin. Med.20174561157116710.1142/S0192415X1750063X 28830214
     [Google Scholar]
  21. DongZ. ZhouJ. ZhangY. Astragaloside-IV alleviates heat-induced inflammation by inhibiting endoplasmic reticulum stress and autophagy.Cell. Physiol. Biochem.201742282483710.1159/000478626 28641278
     [Google Scholar]
  22. LiuJ. MengQ. JingH. ZhouS. Astragaloside IV protects against apoptosis in human degenerative chondrocytes through autophagy activation.Mol. Med. Rep.20171633269327510.3892/mmr.2017.6980 28714008
     [Google Scholar]
  23. SantelA. FullerM.T. Control of mitochondrial morphology by a human mitofusin.J. Cell Sci.2001114586787410.1242/jcs.114.5.867 11181170
     [Google Scholar]
  24. FiladiR. GreottiE. TuracchioG. LuiniA. PozzanT. PizzoP. Mitofusin 2 ablation increases endoplasmic reticulum–mitochondria coupling.Proc. Natl. Acad. Sci. USA201511217E2174E218110.1073/pnas.1504880112 25870285
     [Google Scholar]
  25. BhatiaD. ChungK.P. NakahiraK. Mitophagy-dependent macrophage reprogramming protects against kidney fibrosis.JCI Insight2019423e13282610.1172/jci.insight.132826 31639106
     [Google Scholar]
  26. BuchaS. MukhopadhyayD. BhattacharyyaN.P. E2F1 activates MFN2 expression by binding to the promoter and decreases mitochondrial fission and mitophagy in HeLa cells.FEBS J.2019286224525454110.1111/febs.14980 31276298
     [Google Scholar]
/content/journals/cmm/10.2174/0115665240310818240531080353
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Astragaloside IV Protects Against Podocyte Injury by Upregulating Mitophagy via Mfn2/Pink1/Parkin Axis
Current Molecular Medicine 25, 871 (2025); https://doi.org/10.2174/0115665240310818240531080353
/content/journals/cmm/10.2174/0115665240310818240531080353
/content/journals/cmm/10.2174/0115665240310818240531080353
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  • Article Type:     Research Article
Keyword(s): Astragaloside IV; FSGS; glomerular filtration; mitofusin 2; mitophagy; podocyte

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