Huangqi Guizhi Wuwu Decoction attenuates Podocyte cytoskeletal protein damage in IgA nephropathy rats by regulating AT1R/Nephrin/c-Abl pathway.

Abstract

ETHNOPHARMACOLOGICAL RELEVANCE:

Huangqi Guizhi Wuwu Decoction(HQGZWWD) is a Traditional Chinese Medicine formula from Synopsis of Golden Chamber used to treat blood arthralgia. According to the principle that the same treatment can be used for different diseases, HQGZWWD has proven effective for IgA nephropathy (IgAN) associated with spleen and kidney yang deficiency.

AIM OF THE STUDY:

In this study, we investigated the mechanism by which HQGZWWD alleviates proteinuria and protects renal function in rats with IgAN by regulating the AT1R/Nephrin/c-Abl pathway.

METHODS:

Rats were randomly divided into six groups: control, IgAN model, IgAN model treated with low-dose HQGZWWD, IgAN model treated with medium-dose HQGZWWD, IgAN model treated with high-dose HQGZWWD, and IgAN model treated with valsartan. IgAN was induced using bovine γ-globulin. We evaluated the mediating effects of HQGZWWD on podocyte cytoskeletal proteins, the AT1R/Nephrin/c-Abl pathway, upstream tumor necrosis factor-α (TNF-α), and TNF-α receptor-1 (TNFR1).

RESULTS:

The IgAN rats displayed proteinuria, IgA deposition in the mesangial region, and podocyte cytoskeletal protein damage. The expression of TNF-α, TNFR1, AT1R, and c-Abl was increased in the IgAN rat kidney, whereas the expression of nephrin, podocin, ACTN4, and phosphorylated nephrin (p-nephrin) was reduced. HQGZWWD treatment significantly alleviated podocyte cytoskeletal protein damage in the IgAN rats, upregulated the expression of nephrin, podocin, and ACTN4, and the colocalized expression of F-actin and nephrin. This study demonstrates that HQGZWWD attenuates podocyte cytoskeletal protein damage by regulating the AT1R-nephrin- c-Abl pathway, upregulating the expression of p-nephrin, and downregulating the expression of AT1R and c-Abl.

CONCLUSIONS:

These results indicate that HQGZWWD attenuates podocyte cytoskeletal protein damage in IgAN rats by regulating the AT1R/Nephrin/c-Abl pathway, providing a potential therapeutic approach for IgAN.

• Authors: Weiwei Liu, Liqiang Shi, Qiang Wan, Yansheng Wu, Di Huang, Jiaoying Ou, Qiuyu Liu, Xin Guan, Yuzhu Yang, Xiaotian Zhang, Jiandong Gao
• Journal: Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie (Biomed Pharmacother) Vol. 142 Pg. 111907 (Oct 2021) ISSN: 1950-6007 [Electronic] France
• PMID: 34339916 (Publication Type: Journal Article)
• Copyright: Copyright © 2021 The Authors. Published by Elsevier Masson SAS.. All rights reserved.

Chemical References

• Actins
• Actn4 protein, rat
• Cytoskeletal Proteins
• Drugs, Chinese Herbal
• Immunoglobulin A
• Intracellular Signaling Peptides and Proteins
• Membrane Proteins
• NPHS2 protein
• Protective Agents
• Receptor, Angiotensin, Type 1
• Receptors, Tumor Necrosis Factor, Type I
• Tnfrsf1a protein, rat
• Tumor Necrosis Factor-alpha
• nephrin
• Actinin
• Proto-Oncogene Proteins c-abl

Topics

• Actinin (genetics, metabolism)
• Actins (metabolism)
• Animals
• Cytoskeletal Proteins (metabolism)
• Disease Models, Animal
• Down-Regulation (drug effects)
• Drugs, Chinese Herbal (chemistry, pharmacology, therapeutic use)
• Glomerulonephritis, IGA (drug therapy, metabolism, pathology, physiopathology)
• Immunoglobulin A (metabolism)
• Intracellular Signaling Peptides and Proteins (genetics, metabolism)
• Male
• Membrane Proteins (genetics, metabolism)
• Podocytes (drug effects)
• Protective Agents (chemistry, pharmacology, therapeutic use)
• Proteinuria (metabolism)
• Proto-Oncogene Proteins c-abl (metabolism)
• Rats, Sprague-Dawley
• Receptor, Angiotensin, Type 1 (genetics, metabolism)
• Receptors, Tumor Necrosis Factor, Type I (genetics, metabolism)
• Signal Transduction (drug effects)
• Tumor Necrosis Factor-alpha (genetics, metabolism)