Nanoparticle-mediated Klotho gene therapy prevents acute kidney injury to chronic kidney disease transition through regulating PPARα signaling in renal tubular epithelial cells.

Klotho is an anti-aging protein produced primarily by tubular epithelial cells (TECs). Down-regulated expression of Klotho in injured TECs plays a key pathogenic role in promoting acute kidney injury (AKI) to chronic kidney disease (CKD) transition, yet therapeutic approaches targeting the restoration of renal Klotho levels remain challenging for clinical application. Here, we synthesize polydopamine-polyethylenimine-l-serine-Klotho plasmid nanoparticles (PPSK NPs), which can safely and selectively deliver the Klotho gene to the injured TECs through binding kidney injury molecule-1 and maintain the expression of Klotho protein.

Activation of Piezo1 downregulates renin in juxtaglomerular cells and contributes to blood pressure homeostasis.

Background: The synthesis and secretion of renin in juxtaglomerular (JG) cells are closely regulated by the blood pressure. To date, however, the molecular identity through which JG cells respond to the blood pressure remains unclear.

Results: Here we discovered that Piezo1, a mechanosensitive ion channel, was colocalized with renin in mouse kidney as well as As4.

Single-cell RNA-sequencing reveals distinct immune cell subsets and signaling pathways in IgA nephropathy.

Background: IgA nephropathy (IgAN) is the most common primary glomerulonephritis globally. Increasing evidence suggests the importance of host immunity in the development of IgAN, but its dynamics during the early stage of IgAN are still largely unclear.

Results: Here we successfully resolved the early transcriptomic changes in immune cells of IgAN by conducting single-cell RNA-sequencing (scRNA-seq) with peripheral blood mononuclear cells.

The Advances of Single-Cell RNA-Seq in Kidney Immunology.

Kidney diseases are highly prevalent and treatment is costly. Immune cells play important roles in kidney diseases; however, it has been challenging to investigate the contribution of each cell type in kidney pathophysiology. Recently, the development of single-cell sequencing technology has allowed the extensive study of immune cells in blood, secondary lymphoid tissues, kidney biopsy and urine samples, helping researchers generate a comprehensive immune cell atlas for various kidney diseases.