Huaier Extract Attenuates Acute Kidney Injury to Chronic Kidney Disease Transition by Inhibiting Endoplasmic Reticulum Stress and Apoptosis via miR-1271 Upregulation

Autor: Jing-Ying Zhao, Yu-Bin Wu
Rok vydání: 2020
Předmět:
0301 basic medicine
Article Subject
Renal function
Apoptosis
Complex Mixtures
CHOP
Pharmacology
urologic and male genital diseases
General Biochemistry
Genetics and Molecular Biology
Cell Line
Mice
03 medical and health sciences
0302 clinical medicine
Downregulation and upregulation
Fibrosis
medicine
Animals
Humans
Endoplasmic Reticulum Chaperone BiP
Heat-Shock Proteins
Trametes
General Immunology and Microbiology
urogenital system
business.industry
Endoplasmic reticulum
Acute kidney injury
General Medicine
Acute Kidney Injury
Endoplasmic Reticulum Stress
medicine.disease
female genital diseases and pregnancy complications
Up-Regulation
Mice
Inbred C57BL
MicroRNAs
030104 developmental biology
Gene Expression Regulation
030220 oncology & carcinogenesis
Disease Progression
Kidney Failure
Chronic
Medicine
business
Transcription Factor CHOP
Research Article
Kidney disease
Zdroj: BioMed Research International, Vol 2020 (2020)
BioMed Research International
ISSN: 2314-6141
2314-6133
DOI: 10.1155/2020/9029868
Popis: Endoplasmic reticulum stress (ERS) is strongly associated with acute kidney injury (AKI) to chronic kidney disease (CKD) transition. Huaier extract (HE) protects against kidney injury; albeit, the underlying mechanism is unknown. We hypothesized that HE reduces kidney injury by inhibiting ERS. In this study, using an AKI-CKD mouse model of ischemia-reperfusion injury (IRI), we evaluated the effect of HE on AKI-CKD transition. We also explored the underlying molecular mechanisms in this animal model and in the HK-2 human kidney cell line. The results showed that HE treatment improved the renal function, demonstrated by a significant decrease in serum creatinine levels after IRI. HE appreciably reduced the degree of kidney injury and fibrosis and restored the expression of the microRNA miR-1271 after IRI. Furthermore, HE reduced the expression of ERS markers glucose-regulated protein 78 (GRP78) and C/EBP homologous protein (CHOP) and inhibited apoptosis in the IRI group. This in vivo effect was supported by in vitro results in which HE inhibited apoptosis and decreased the expression of CHOP and GRP78 induced by ERS. We demonstrated that CHOP is a target of miR-1271. In conclusion, HE reduces kidney injury, probably by inhibiting apoptosis and decreasing the expression of GRP78 and CHOP via miR-1271 upregulation.
Databáze: OpenAIRE
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