Dysregulated Expression of microRNA-21 and Disease-Related Genes in Human Patients and in a Mouse Model of Alport Syndrome

Human Gene Therapy
Jifan GuoShiguang Liu

Abstract

Alport syndrome is a genetic disease caused by mutations in type IV collagen and is characterized by progressive kidney disease. The Col4α3-/- mouse model recapitulates the main features of human Alport syndrome. Previously, it was reported that kidney microRNA-21 (miR-21) expression is significantly increased in Col4α3-/- mice, and administration of anti-miR-21 oligonucleotides (anti-miR-21) attenuates kidney disease progression in Col4α3-/- mice, indicating that miR-21 is a viable therapeutic target for Alport syndrome. However, the expression pattern of miR-21 in the kidneys of patients with human Alport syndrome has not been evaluated. Paraffin-embedded kidney specimens were obtained from 27 patients with Alport syndrome and from 10 normal controls. They were evaluated for miR-21 expression and for in situ hybridization and mRNA expression by quantitative polymerase chain reaction. In addition, anti-miR-21 was administrated to Col4α3-/- mice at different stages of disease, and changes in proteinuria, kidney function, and survival were monitored. Transcriptomic analysis of mouse kidney was conducted using RNA sequencing. miR-21 expression was significantly elevated in kidney specimens from patients with Alport syndrome compa...Continue Reading

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Feb 28, 2020·Circulation Research·Cheng-Kai HuangThomas Thum
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Methods Mentioned

BETA
biopsies
biopsy
enzyme-linked immunosorbent assay
RNA-Seq

Software Mentioned

Omicsoft Aligner
GraphPad Prism
GraphPad
Omicsoft Array Studio

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