GABA alleviates high glucose-induced podocyte injury through dynamically altering the expression of macrophage M1/M2-derived exosomal miR-21a-5p/miR-25-3p.

Podocyte injury is the main clinical pathological feature of diabetic kidney disease (DKD). The studies showed that DKD is associated with the polarization of macrophages to different types (M1 or M2) and the inflammatory processes which they mediate. It is a hot research topic in the treatment of DKD that find and intervene genes which related to M1/M2 phenotype.

Cell Type-Specific Predictive Models Perform Prioritization of Genes and Gene Sets Associated With Autism.

Bulk transcriptomic analyses of autism spectrum disorder (ASD) have revealed dysregulated pathways, while the brain cell type-specific molecular pathology of ASD still needs to be studied. Machine learning-based studies can be conducted for ASD, prioritizing high-confidence gene candidates and promoting the design of effective interventions. Using human brain nucleus gene expression of ASD and controls, we construct cell type-specific predictive models for ASD based on individual genes and gene sets, respectively, to screen cell type-specific ASD-associated genes and gene sets.

Mitochondrial oxidative stress activates COX-2/mPGES-1/PGE2 cascade induced by albumin in renal proximal tubular cells.

COX-2/mPGES-1/PGE2 cascade is of importance in the pathogenesis of kidney injury. Meanwhile, recent studies documented a detrimental role of mitochondrial oxidative stress in kidney diseases. The present study was undertaken to investigate the role of mitochondrial oxidative stress in albumin-induced activation of COX-2/mPGES-1/PGE2 cascade in renal proximal tubular cells.

Activation of COX-2/mPGES-1/PGE2 Cascade via NLRP3 Inflammasome Contributes to Albumin-Induced Proximal Tubule Cell Injury.

Background/aims: The activation of NOD-like receptor family, pyrin domain containing3 (NLRP3) inflammasome has been shown to be positively correlated with the severity of proteinuria in chronic kidney disease (CKD) patients. Prostaglandin E2 (PGE2), an important inflammatory mediator, is also involved in various kidney injuries. The aim of the present study was to investigate the involvement of NLRP3 inflammasome and PGE2 synthetic pathway in albumin-induced renal tubular injury.

Albuminuria confers renal resistance to loop diuretics via the stimulation of NLRP3 inflammasome/prostaglandin signaling in thick ascending limb.

Renal resistance to loop diuretics is a frequent complication in a number of kidney disease patients with elusive mechanism. Employing human renal biopsy specimens, albumin overload mouse model, and primary cultures of mouse renal tubular cells, albuminuria effect on NKCC2 expression and function and the underlying mechanisms were investigated. In the renal biopsy specimens of albuminuric patients, we found that NKCC2 was significantly downregulated with a negative correlation with albuminuria severity as examined by immunohistochemistry.

Albuminuria enhances NHE3 and NCC via stimulation of mitochondrial oxidative stress/angiotensin II axis.

Imbalance of salt and water is a frequent and challenging complication of kidney disease, whose pathogenic mechanisms remain elusive. Employing an albumin overload mouse model, we discovered that albuminuria enhanced the expression of NHE3 and NCC but not other transporters in murine kidney in line with the stimulation of angiotensinogen (AGT)/angiotensin converting enzyme (ACE)/angiotensin (Ang) II cascade. In primary cultures of renal tubular cells, albumin directly stimulated AGT/ACE/Ang II and upregulated NHE3 and NCC expression.

Albumin impairs renal tubular tight junctions via targeting the NLRP3 inflammasome.

Proteinuria is, not only a hallmark of glomerular disease, but also a contributor to kidney injury. However, its pathogenic mechanism is still elusive. In the present study, the effects of albumin on renal tubular tight junctions and the potential molecular mechanisms of those effects were investigated.

Mitochondrial dysfunction confers albumin-induced NLRP3 inflammasome activation and renal tubular injury.

Proteinuria is involved in the development of tubular lesions and in the progressive loss of renal function in chronic kidney diseases via uncertain mechanisms. Growing evidence suggests a pathogenic role of mitochondrial dysfunction in chronic kidney diseases. Therefore, the present study aimed to define the roles of mitochondria in proteinuria-induced renal tubular injury and their underlying mechanisms.

NLRP3 inflammasome mediates albumin-induced renal tubular injury through impaired mitochondrial function.

Proteinuria serves as a direct causative factor of renal tubular cell injury and is highly associated with the progression of chronic kidney disease via uncertain mechanisms. Recently, evidence demonstrated that both NLRP3 inflammasome and mitochondria are involved in the chronic kidney disease progression. The present study was undertaken to examine the role of NLRP3 inflammasome/mitochondria axis in albumin-induced renal tubular injury.

Activation of ERK1/2 by NADPH oxidase-originated reactive oxygen species mediates uric acid-induced mesangial cell proliferation.

Hyperuricemia is associated with kidney complications including glomerulosclerosis and mesangial cell (MC) proliferation by poorly understood mechanisms. The present study investigated the underlying mechanisms that mediate uric acid (UA)-induced MC proliferation. A rat MC line, HBZY-1, was treated with various concentrations of UA in the presence or absence of a specific extracellular-regulated protein kinase 1/2 (ERK1/2) inhibitor (U0126), apocynin.