The critical role of endoplasmic reticulum stress and the stimulator of interferon genes (STING) pathway in kidney fibrosis.

Endoplasmic reticulum (ER) stress is a condition in which the ER is overwhelmed and unable to manage its protein load properly. The precise activation mechanisms and role of ER stress in kidney disease remain unclear. To study this, we performed unbiased transcriptomics analysis to demonstrate ER stress in kidneys of patients with chronic kidney disease and in mouse models of acute and chronic kidney injury (cisplatin and unilateral ureteral obstruction and reanalyzed previously published data on folic acid and mitochondrial transcription factor A(TFAM) knockout mice).

TET2 germline variants promote kidney disease by impairing DNA repair and activating cytosolic nucleotide sensors.

Genome-wide association studies (GWAS) have identified over 800 loci associated with kidney function, yet the specific genes, variants, and pathways involved remain elusive. By integrating kidney function GWAS with human kidney expression and methylation quantitative trait analyses, we identified Ten-Eleven Translocation (TET) DNA demethylase 2 (TET2) as a novel kidney disease risk gene. Utilizing single-cell chromatin accessibility and CRISPR-based genome editing, we highlight GWAS variants that influence TET2 expression in kidney proximal tubule cells.

Genetic Studies Highlight the Role of TET2 and INO80 in DNA Damage Response and Kidney Disease Pathogenesis.

Genome-wide association studies (GWAS) have identified over 800 loci associated with kidney function, yet the specific genes, variants, and pathways involved remain elusive. By integrating kidney function GWAS, human kidney expression and methylation quantitative trait analyses, we identified Ten-Eleven Translocation (TET) DNA demethylase 2: TET2 as a novel kidney disease risk gene. Utilizing single-cell chromatin accessibility and CRISPR-based genome editing, we highlight GWAS variants that influence expression in kidney proximal tubule cells.

SerpinA3K Deficiency Reduces Oxidative Stress in Acute Kidney Injury.

We previously showed that SerpinA3K is present in urine from rats and humans with acute kidney injury (AKI) and chronic kidney disease (CKD). However, the specific role of SerpinA3K during renal pathophysiology is unknown. To begin to understand the role of SerpinA3K on AKI, SerpinA3K-deficient (KOSA3) mice were studied 24 h after inducing ischemia/reperfusion (I/R) and compared to wild type (WT) mice.

Repeated Episodes of Ischemia/Reperfusion Induce Heme-Oxygenase-1 (HO-1) and Anti-Inflammatory Responses and Protects against Chronic Kidney Disease.

Preconditioning episodes of ischemia/reperfusion (IR) induce protection against acute kidney injury (AKI), however their long-term effect still unknown. We evaluated AKI to chronic kidney disease (CKD) transition, after three-mild or three-severe episodes of IR. AKI was induced by single bilateral IR (1IR), or three episodes of IR separated by 10-day intervals (3IR) of mild (20 min) or severe (45 min) ischemia.

Urinary serpin-A3 is an early predictor of clinical response to therapy in patients with proliferative lupus nephritis.

We have previously reported that urinary excretion of serpin-A3 (uSerpA3) is significantly elevated in patients with active lupus nephritis (LN). Here, we evaluated the course of uSerpA3 during the first year of treatment and its association with response to therapy in patients with proliferative LN. The observational longitudinal study included 60 Mexican adults with proliferative LN followed during the first year after LN flare.

Sirtuin 7 Deficiency Reduces Inflammation and Tubular Damage Induced by an Episode of Acute Kidney Injury.

Acute kidney injury (AKI) is a public health problem worldwide. Sirtuins are a family of seven NAD+-dependent deacylases, Overexpression of Sirtuin 1, 3, and 5 protect against AKI. However, the role of Sirtuin 7 (Sirt7) in AKI is not known.

Early triggers of moderately high-fat diet-induced kidney damage.

Most of the obesity murine models inducing renal injury use calorie-enriched foods, where fat represents 60% of the total caloric supply, however, this strategy doubles the standard proportion of fat ingestion in obese patients. Therefore, it is crucial to study the impact of a high-fat intake on kidney physiology that resembles common obesity in humans to understand the trigger mechanisms of the long-term consequences of overweight and obesity. In this study, we analyzed whether chronic feeding with a moderately high fat diet (MHFD) representing 45% of total calories, may induce kidney function and structural injury compared to C57BL/6 mice fed a control diet.

Vegfa promoter gene hypermethylation at HIF1α binding site is an early contributor to CKD progression after renal ischemia.

Chronic hypoxia is a major contributor to Chronic Kidney Disease (CKD) after Acute Kidney Injury (AKI). However, the temporal relation between the acute insult and maladaptive renal response to hypoxia remains unclear. In this study, we analyzed the time-course of renal hemodynamics, oxidative stress, inflammation, and fibrosis, as well as epigenetic modifications, with focus on HIF1α/VEGF signaling, in the AKI to CKD transition.

Role of KLHL3 and dietary K in regulating KS-WNK1 expression.

The physiological role of the shorter isoform of with no lysine kinase (WNK)1 that is exclusively expressed in the kidney (KS-WNK1), with particular abundance in the distal convoluted tubule, remains elusive. KS-WNK1, despite lacking the kinase domain, is nevertheless capable of stimulating the NaCl cotransporter, apparently through activation of WNK4. It has recently been shown that a less severe form of familial hyperkalemic hypertension featuring only hyperkalemia is caused by missense mutations in the WNK1 acidic domain that preferentially affect cullin 3 (CUL3)-Kelch-like protein 3 (KLHL3) E3-induced degradation of KS-WNK1 rather than that of full-length WNK1.

An integrative view of serpins in health and disease: the contribution of SerpinA3.

Serpins are a superfamily of proteins characterized by their common function as serine protease inhibitors. So far, 36 serpins from nine clades have been identified. These proteins are expressed in all the organs and are involved in multiple important functions such as the regulation of blood pressure, hormone transport, insulin sensitivity, and the inflammatory response.

Resilience to acute kidney injury in offspring of maternal protein restriction.

Protein restriction (PR) during pregnancy induces morphofunctional alterations related to deficient nephrogenesis. We studied the renal functional and morphological significance of PR during pregnancy and/or lactation in adult male rat offspring and the repercussions on acute kidney injury (AKI) severity. Female rats were randomly assigned to the following groups: control diet during pregnancy and lactation (CC), control diet during pregnancy and PR diet during lactation (CR), PR during pregnancy and control diet during lactation (RC), and PR during pregnancy and lactation (RR).

SerpinA3 in the Early Recognition of Acute Kidney Injury to Chronic Kidney Disease (CKD) transition in the rat and its Potentiality in the Recognition of Patients with CKD.

Recognizing patients at early phases of chronic kidney disease (CKD) is difficult, and it is even more challenging to predict acute kidney injury (AKI) and its transition to CKD. The gold standard to timely identify renal fibrosis is the kidney biopsy, an invasive procedure not usually performed for this purpose in clinical practice. SerpinA3 was identified by high-resolution-mass-spectrometry in urines from animals with CKD.

Gender Differences in the Acute Kidney Injury to Chronic Kidney Disease Transition.

This study evaluated if there is a sexual dimorphism in the acute kidney injury (AKI) to chronic kidney disease (CKD) transition and the time-course of the potential mechanisms involved in the dimorphic response. Female and male rats were divided into sham-operated or underwent 45-min renal ischemia (F + IR, and M + IR). All groups were studied at 24-h and 1, 2, 3, or 4-months post-ischemia.

Semaphorin 3C Released from a Biocompatible Hydrogel Guides and Promotes Axonal Growth of Rodent and Human Dopaminergic Neurons.

Cell therapy in experimental models of Parkinson's disease replaces the lost dopamine neurons (DAN), but we still need improved methods to guide dopaminergic axons (DAx) of grafted neurons to make proper connections. The protein Semaphorin 3C (Sema3C) attracts DAN axons and enhances their growth. In this work, we show that the hydrogel PuraMatrix, a self-assembling peptide-based matrix, incorporates Sema3C and releases it steadily during 4 weeks.

Balance and motor coordination are not fully developed in 7-year-old blind children.

Visually impaired children show difficulties in recognizing their own bodies, objects around then and the spatial parameters that are essential for independent movement. This study analyzes the neuro-psychomotor development of a group of congenitally visually impaired children as compared to children with normal sight. We have evaluated two groups of seven-year-olds by means of neurological evolution examination (NEE).