Tumor necrosis factor-stimulated gene-6 inhibits endoplasmic reticulum stress in the ischemic mouse kidney.

Kidney tissue injury in renal artery stenosis (RAS) involves inflammation, endoplasmic reticulum stress (ERS), and mitochondria damage. Tumor necrosis factor-stimulated gene-6 (TSG-6), an endogenous reparative molecule, may decrease ERS and improve renal function. To assess its impact on the stenotic murine kidney, we injected TSG-6 or vehicle for two weeks in mice with RAS.

Gastrodin Attenuates Neuroinflammation and Injury in Young Rats with LiCl/Pilocarpine-Induced Status Epilepticus.

Status epilepticus is a severe neurological emergency that often leads to long-term neuronal damage and functional impairment. Gastrodin is a compound widely used in traditional Chinese medicine with potential neuroprotective effects. This study aims to investigate the effects of GAS on neuroinflammation and injury caused by LiCl/pilocarpine-induced SE in young rats.

Kidney injury: the spleno-renal connection and splenic tyrosine kinase.

Kidney injury is a major medical burden and one of the most common reasons for hospitalization and poor life quality. Kidney injury can include acute kidney injury, chronic kidney disease, and immune-mediated kidney diseases most of which have no definitive therapy. The spleen is a secondary lymphoid organ in the reticuloendothelial system that plays an important role in protecting the body from various diseases.

Altered immune cell phenotypes within chronically ischemic human kidneys distal to occlusive renal artery disease.

Renal artery stenosis (RAS) is a major cause of ischemic kidney disease, which is largely mediated by inflammation. Mapping the immune cell composition in ischemic kidneys might provide useful insight into the disease pathogenesis and uncover therapeutic targets. We used mass cytometry (CyTOF) to explore the single-cell composition in a unique data set of human kidneys nephrectomized due to chronic occlusive vascular disease (RAS, = 3), relatively healthy donor kidneys ( = 6), and unaffected sections of kidneys with renal cell carcinoma (RCC, = 3).

Clinical and pathological characteristics of acute kidney injury caused by diquat poisoning.

: Diquat poisoning leads to kidney injury, hepatotoxicity, rhabdomyolysis, gastrointestinal hemorrhage, and respiratory failure. Diquat has high mortality and no specific antidote. The pathology of acute kidney injury caused by diquat poisoning has been mainly investigated in animal studies and autopsies, and typically shows renal tubular necrosis.

Obesity and dyslipidemia are associated with partially reversible modifications to DNA hydroxymethylation of apoptosis- and senescence-related genes in swine adipose-derived mesenchymal stem/stromal cells.

Background: Obesity dysregulates key biological processes underlying the functional homeostasis, fate decisions, and reparative potential of mesenchymal stem/stromal cells (MSCs). Mechanisms directing obesity-induced phenotypic alterations in MSCs remain unclear, but emerging drivers include dynamic modification of epigenetic marks, like 5-hydroxymethylcytosine (5hmC). We hypothesized that obesity and cardiovascular risk factors induce functionally relevant, locus-specific changes in 5hmC of swine adipose-derived MSCs and evaluated their reversibility using an epigenetic modulator, vitamin-C.

Metabolic Syndrome Induces Epigenetic Alterations in Mitochondria-Related Genes in Swine Mesenchymal Stem Cells.

Autologous mesenchymal stem/stromal cells (MSCs) have demonstrated important therapeutic effects in several diseases. Cardiovascular risk factors may impair MSC mitochondrial structure and function, but the underlying mechanisms remain unknown. We hypothesized that metabolic syndrome (MetS) induces epigenetic alterations in mitochondria-related genes in swine MSCs.

Autologous Extracellular Vesicles Attenuate Cardiac Injury in Experimental Atherosclerotic Renovascular Disease More Effectively Than Their Parent Mesenchymal Stem/Stromal Cells.

Atherosclerotic renovascular disease (RVD) leads to hypertension, chronic kidney disease (CKD), and heart disease. Intrarenal delivery of mesenchymal stem cells (MSCs) and MSC-derived extracellular vesicles (EVs) attenuate renal injury and suppress release of inflammatory cytokines in porcine RVD. We hypothesized that this strategy would also be useful for cardioprotection.

Effect of Hypoxia Preconditioning on the Regenerative Capacity of Adipose Tissue Derived Mesenchymal Stem Cells in a Model of Renal Artery Stenosis.

Atherosclerotic renal artery stenosis (ARAS) is associated with irreversible parenchymal renal disease and regenerative stem cell therapies may improve renal outcomes. Hypoxia preconditioning (HPC) may improve the regenerative functions of adipose tissue-derived mesenchymal stem cells (AMSC) by affecting DNA 5-hydroxymethylcytosine (5hmC) marks in angiogenic genes. Here, we investigated using a porcine ARAS model, whether growth of ARAS AMSCs in hypoxia (Hx) versus normoxia (Nx) would enhance renal tissue repair, and comprehensively analyze how HPC modifies DNA hydroxymethylation compared to untreated ARAS and healthy/normal pigs (n=5 each).

Effects of Elamipretide on Autophagy in Renal Cells of Pigs with Metabolic Syndrome.

Autophagy eliminates excessive nutrients and maintains homeostasis. Obesity and metabolic syndrome (MetS) dysregulate autophagy, possibly partly due to mitochondria injury and inflammation. Elamipretide (ELAM) improves mitochondrial function.

Exogenous pericyte delivery protects the mouse kidney from chronic ischemic injury.

Pericytes are considered reparative mesenchymal stem cell-like cells, but their ability to ameliorate chronic ischemic kidney injury is unknown. We hypothesized that pericytes would exhibit renoprotective effects in murine renal artery stenosis (RAS). Porcine kidney-derived pericytes (5 × 10) or vehicle were injected into the carotid artery 2 wk after the induction of unilateral RAS in mice.

Renal Ischemia Induces Epigenetic Changes in Apoptotic, Proteolytic, and Mitochondrial Genes in Swine Scattered Tubular-like Cells.

Background: Scattered tubular-like cells (STCs) are dedifferentiated renal tubular cells endowed with progenitor-like characteristics to repair injured parenchymal cells. STCs may be damaged and rendered ineffective by renal artery stenosis (RAS), but the underlying processes remain unclear. We hypothesized that RAS alters the epigenetic landscape on DNA and the ensuing gene transcriptional profile of swine STCs.

Microvascular remodeling and altered angiogenic signaling in human kidneys distal to occlusive atherosclerotic renal artery stenosis.

Background: Renal artery stenosis (RAS) is an important cause of chronic kidney disease and secondary hypertension. In animal models, renal ischemia leads to downregulation of growth factor expression and loss of intrarenal microcirculation. However, little is known about the sequelae of large-vessel occlusive disease on the microcirculation within human kidneys.

Selective kidney targeting increases the efficacy of mesenchymal stromal/stem cells for alleviation of murine stenotic-kidney senescence and damage.

Chronic ischemia triggers senescence in renal tubules and at least partly mediates kidney dysfunction and damage through a p16 -related mechanism. We previously showed that mesenchymal stromal/stem cells (MSCs) delivered systemically do not effectively decrease cellular senescence in stenotic murine kidneys. We hypothesized that selective MSC targeting to injured kidneys using an anti-KIM1 antibody (KIM-MSC) coating would enhance their ability to abrogate cellular senescence in murine renal artery stenosis (RAS).

Extracellular Vesicles as Theranostic Tools in Kidney Disease.

Extracellular vesicles are important vectors for cell-cell communication and show potential value for diagnosis and treatment of kidney diseases. The pathologic diagnosis of kidney diseases relies on kidney biopsy, whereas collection of extracellular vesicles from urine or circulating blood may constitute a less invasive diagnostic tool. In particular, urinary extracellular vesicles released mainly from resident kidney cells might provide an alternative tool for detection of kidney injury.

Effects of obesity on reparative function of human adipose tissue-derived mesenchymal stem cells on ischemic murine kidneys.

Introduction: Obesity is a health burden that impairs cellular processes. Mesenchymal stem/stromal cells (MSCs) are endowed with reparative properties and can ameliorate renal injury. Obesity impairs human MSC function in-vitro, but its effect on their in-vivo reparative potency remains unknown.

Impaired immunomodulatory capacity in adipose tissue-derived mesenchymal stem/stromal cells isolated from obese patients.

Immune-modulatory properties of adipose tissue-derived mesenchymal stem/stromal cells (MSCs) might be susceptible to metabolic disturbances. We hypothesized that the immune-modulatory function of MSCs might be blunted in obese human subjects. MSCs were collected from abdominal subcutaneous fat of obese and lean subjects during bariatric or kidney donation surgeries, respectively.

Renal Revascularization Attenuates Myocardial Mitochondrial Damage and Improves Diastolic Function in Pigs with Metabolic Syndrome and Renovascular Hypertension.

Percutaneous transluminal renal angioplasty (PTRA) may improve cardiac function in renovascular hypertension (RVH), but its effect on the biological mechanisms implicated in cardiac damage remains unknown. We hypothesized that restoration of kidney function by PTRA ameliorates myocardial mitochondrial damage and preserves cardiac function in pigs with metabolic syndrome (MetS) and RVH. Pigs were studied after 16 weeks of MetS+RVH, MetS+RVH treated 4 weeks earlier with PTRA, and Lean and MetS Sham controls (n=6 each).

Progressive Cellular Senescence Mediates Renal Dysfunction in Ischemic Nephropathy.

Background: Peripheral vascular diseases may induce chronic ischemia and cellular injury distal to the arterial obstruction. Cellular senescence involves proliferation arrest in response to stress, which can damage neighboring cells. Renal artery stenosis (RAS) induces stenotic-kidney dysfunction and injury, but whether these arise from cellular senescenceand their temporal pattern remain unknown.

The Micro-RNA Cargo of Extracellular Vesicles Released by Human Adipose Tissue-Derived Mesenchymal Stem Cells Is Modified by Obesity.

Obesity is a chronic disease that interferes with normal repair processes, including adipose mesenchymal stem/stromal cells (ASCs) function. ASCs produce extracellular vesicles (EVs) that activate a repair program in recipient cells partly via their micro-RNA (miRNA) cargo. We hypothesized that obesity alters the miRNA expression profile of human ASC-derived EVs, limiting their capacity to repair injured cells.

Mesenchymal Stem/Stromal Cell-Derived Extracellular Vesicles Elicit Better Preservation of the Intra-Renal Microvasculature Than Renal Revascularization in Pigs with Renovascular Disease.

Background: Percutaneous transluminal renal angioplasty (PTRA) confers clinical and mortality benefits in select 'high-risk' patients with renovascular disease (RVD). Intra-renal-delivered extracellular vesicles (EVs) released from mesenchymal stem/stromal cells (MSCs) protect the kidney in experimental RVD, but have not been compared side-by-side to clinically applied interventions, such as PTRA. We hypothesized that MSC-derived EVs can comparably protect the post-stenotic kidney via direct tissue effects.