4.7 Article

MicroRNA-23b-3p Deletion Induces an IgA Nephropathy-like Disease Associated with Dysregulated Mucosal IgA Synthesis

Journal

JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY
Volume 32, Issue 10, Pages 2561-2578

Publisher

AMER SOC NEPHROLOGY
DOI: 10.1681/ASN.2021010133

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The study revealed that miR-23b is downregulated in IgAN and may play a crucial role in kidney disease and the development of IgAN. It suggests that miR-23b could be a novel therapeutic target for treating IgAN in the future.
Background IgA nephropathy (IgAN) is the most common primary GN worldwide. Circulating immune complexes form that are prone to deposition in the mesangium, where they trigger glomerular inflammation. A growing body of evidence suggests that dysregulated expression of microRNAs in IgAN may play a significant role in establishing the disease phenotype. Methods We generated single miR-23b-3p(miR-23b) knockout mice using CRISPR-Cas9. Results In humans, miR-23b levels are downregulated in kidney biopsies and sera of patients with IgAN, and serum miR-23b levels are negatively correlated with serum IgA1 levels. We show that miR-23b2/2 mice develop an IgAN-like phenotype of mesangial IgA and C3 deposition associated with development of albuminuria, hypertension, an elevated serum creatinine, and dysregulated mucosal IgA synthesis. Dysregulation of IgA production is likely mediated by the loss of miR-23b-mediated suppression of activation-induced cytidine deaminase in mucosal B cells. In addition, we show that loss of miR-23b increases the susceptibility of the kidney to progressive fibrosis through loss of regulation of expression of gremlin 2 and IgA accumulation through downregulation of the transferrin receptor. Conclusions Our findings suggest an indispensable role for miR-23b in kidney disease, and in particular, IgAN. miR-23b may in the future offer a novel therapeutic target for the treatment of IgAN.

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