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Alleviation by Mahuang Fuzi and Shenzhuo Decoction in High Glucose-Induced Podocyte Injury by Inhibiting the Activation of Wnt/-Catenin Signaling Pathway, Resulting in Activation of Podocyte Autophagy

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Date 2020 Sep 23
PMID 32963573
Citations 8
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Abstract

Background: Organ fibrosis is a common endpoint of a variety of diseases. Many studies have shown that the pathogenesis of diabetic kidney disease (DKD) is related to the excessive activation of the Wnt/-catenin signaling pathway on podocytes, so the treatment of DKD starts from this signaling pathway. At the same time, DKD, as a metabolic disease, has many connections related to podocyte autophagy.

Objectives: We experimented the effects of Mahuang Fuzi and Shenzhuo decoction (MFSD) which is the combination of Mahuang Fuzi decoction and Shenzhuo decoction in traditional Chinese medicine compounds used "The Golden Chamber" in high glucose-induced podocytes, determined whether this effect was related to Wnt/-catenin signaling pathway, and further investigated the relationship between this effect and autophagy.

Methods: The mice podocytes were stimulated by using 30 mmol/L of high glucose and serum containing MFSD or Wnt/-catenin signaling pathway inhibitor DKK1 (100 ng/ml) was used to intervene podocytes before high glucose stimulation. Podocyte injury-related proteins, Wnt/-catenin signaling pathway-related proteins, and autophagy-related proteins were detected by using western blotting and immunofluorescence analysis.

Results: Our results showed that DKK1 and MFSD treatment significantly upregulated the protein expressions of nephrin, podocin, podocalyxin, and podoplanin in high glucose-induced podocytes and downregulated the -catenin protein expression. Furthermore, the protein expressions of beclin1, LC3B, and P62 were also significantly increased in high glucose-induced podocytes.

Conclusion: Our experiments confirmed that the destruction of podocytes in DKD is related to the excessive activation of Wnt/-catenin signaling pathway and the inhibition of autophagy after activation. MFSD treatment can inhibit the activation of Wnt/-catenin signaling pathway in podocytes stimulated by high glucose and helpful in reducing the podocyte injury. This protective mechanism can be related to the enhancement of podocyte autophagy by MFSD treatment.

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References
1.
Vuong L, Iomini C, Balmer S, Esposito D, Aaronson S, Mlodzik M . Kinesin-2 and IFT-A act as a complex promoting nuclear localization of β-catenin during Wnt signalling. Nat Commun. 2018; 9(1):5304. PMC: 6294004. DOI: 10.1038/s41467-018-07605-z. View

2.
Singh S, Mishra A, Mohanbhai S, Tiwari V, Chaturvedi R, Khurana S . Axin-2 knockdown promote mitochondrial biogenesis and dopaminergic neurogenesis by regulating Wnt/β-catenin signaling in rat model of Parkinson's disease. Free Radic Biol Med. 2018; 129:73-87. DOI: 10.1016/j.freeradbiomed.2018.08.033. View

3.
Bernkopf D, Bruckner M, Hadjihannas M, Behrens J . An aggregon in conductin/axin2 regulates Wnt/β-catenin signaling and holds potential for cancer therapy. Nat Commun. 2019; 10(1):4251. PMC: 6751202. DOI: 10.1038/s41467-019-12203-8. View

4.
Wang M, Chen D, Chen L, Cao G, Zhao H, Liu D . Novel inhibitors of the cellular renin-angiotensin system components, poricoic acids, target Smad3 phosphorylation and Wnt/β-catenin pathway against renal fibrosis. Br J Pharmacol. 2018; 175(13):2689-2708. PMC: 6003649. DOI: 10.1111/bph.14333. View

5.
Yang T, Chen Y, Liu J, Zhao H, Vaziri N, Guo Y . Natural products against renin-angiotensin system for antifibrosis therapy. Eur J Med Chem. 2019; 179:623-633. DOI: 10.1016/j.ejmech.2019.06.091. View