Diabetic nephropathy pathological pathways

Podocyte inflammatory injury has been indicated to play a pivotal role in the occurrence and development of diabetic nephropathy (DN). However, the pathogenesis of inflammation remains unclear. Recent researches have shown that GDF-15, a member of the transforming growth factor-β superfamily, were elevated under pathological conditions, such as myocardial ischemia, cancer, as well as inflammation. Here, we demonstrated that GDF-15 could alleviate podocyte inflammatory injury by modulating the NF-κB pathway...

Diabetic nephropathy (DN) is one of the complications of diabetes mellitus and the main cause of end-stage renal disease (ESRD), which is a serious threat to human health. In DN, mesangial cells (MCs) are a critical target cell that perform a variety of key functions, and abnormal proliferation of MCs is a common and prominent pathological change in DN. In recent years, the investigation of Chinese medicine interventions for DN has increased significantly in recent years due to the many potential adverse effects and controversies associated with the treatment of DN with Western medicines...

BACKGROUND: The chemokine ligand CCL2 and its cognate receptor CCR2 have been implicated in the pathogenesis of a wide variety of diseases. Hence, the inhibition of the CCL2/CCR2 signaling pathway has been of great attention in recent studies. Among suggested medications, statins known as HMG-COA reductase inhibitors with their pleiotropic effects are widely under investigation. METHOD: A comprehensive literature search on Scopus and PubMed databases was conducted using the keywords 'CCL2', 'CCR2', 'monocyte chemoattractant protein-1', 'HMG-COA reductase inhibitor', and 'statin'...

OBJECTIVE: To explore the mechanisms mediating the protective effect of carnosine against nephropathy in rats with diabetes mellitus (DM). METHODS: Rat models of DM established by high-fat diet feeding and streptozotocin injection were randomized into DM group and 3 treatment groups with daily carnosine treatment at 100, 300, and 900 mg/kg. Body weight and blood glucose level changes of the rats were measured regularly. After the treatment, 24-h urine, serum samples and kidneys of the rats were collected to measure urine volume, urine protein content, blood creatinine, and kidney mass; renal pathology was observed using HE staining, and MDA content and SOD activity in the kidney tissues were detected...

Diabetic nephropathy (DN) is a common diabetic complication. Studies show that mitophagy inhibition induced-ferroptosis plays a crucial role in DN progression. UHRF1 is associated with mitophagy and is highly expression in DN patients, however, the effect of UHRF1 on DN is still unclear. Thus, in this study, we aimed to investigate whether UHRF1 involves DN development by the mitophagy/ferroptosis pathway. We overexpressed UHRF1 using an adeno-associated virus 9 (AAV9) system in high-fat diet/streptozotocin-induced diabetic mice...

The kidneys have a high level of Netrin-1 expression, which protects against some acute and chronic kidney disorders. However, it is yet unknown how Netrin-1 affects renal proximal tubule cells in diabetic nephropathy (DN) under pathological circumstances. Research has shown that autophagy protects the kidneys in animal models of renal disease. In this study, we looked at the probable autophagy regulation mechanism of Netrin-1 and its function in the pathogenesis of DN. We proved that in HK-2 cell, high blood sugar levels caused Netrin-1 to be downregulated, which then triggered the Akt/mTOR signaling pathway and enhanced cell death and actin cytoskeleton disruption...

Chromium picolinate (CP) is an organic compound that has long been used to treat diabetes. Our previous studies found CP could relieve diabetic nephropathy. Thus, we speculate that it might have a positive effect on diabetic testicular injury. In this study, a diabetic rat model was established, and then the rats were treated with CP for 8 weeks. We found that the levels of blood glucose, food, and water intake were reduced, and body weight was enhanced in diabetic rats after CP supplementation. Meanwhile, in CP treatment groups, the levels of male hormone and sperm parameters were improved, the pathological structure of the testicular tissue was repaired, and testicular fibrosis was inhibited...

BACKGROUND: Astragalus polysaccharide (APS) is a major bioactive component of the Chinese herb astragalus, with well-established protective effects on the kidney. However, the effect of APS on diabetic nephropathy (DN) is unclear. METHODS: Long non-coding RNA (lncRNA) expression profiles in kidney samples from control, db/db, and APS-treated db/db mice were evaluated using RNA high-throughput sequencing techniques. Additionally, rat renal tubular epithelial (NRK-52E) cells were cultured in high glucose (HG) media...

Glomerulosclerosis and tubulointerstitial fibrosis (TIF) are closely involved in the development of diabetic nephropathy (DN). Moreover, the development of TIF is closely related to epithelial-to-mesenchymal transition (EMT). Tanshinone IIA (Tan) has various pharmacological effects, especially the anti-fibrotic effect. And it is mainly used in the clinical treatment of cardiovascular diseases. Currently, the protective effect of Tan on DN and its possible mechanism have not been clearly elucidated. Our previous studies illustrated that Tan could improve the EMT of HK-2 cells induced by high glucose by regulating the vitamin D receptor (VDR)/Wnt/β-catenin pathway...

INTRODUCTION: Oxidative stress is pivotal in advancing diabetic nephropathy (DN). Salvianolic acid B (SAB), derived from Radix Salviae miltiorrhizae, exhibits renoprotective effects. However, the mechanisms underlying its action in DN are not fully elucidated. This study explores SAB's protective effect on DN, focusing on its antioxidative properties in glomerular mesangial cells. METHODS: The renoprotective effects of various SAB dosages on DN rats were assessed by evaluating kidney tissue pathological alterations through hematoxylin and eosin, periodic acid-Schiff, Masson, TUNEL staining, and kidney function through biochemical detection...

INTRODUCTION: Diabetic kidney disease (DKD), one of the leading causes of end-stage renal disease, has complex pathogenic mechanisms and few effective clinical therapies. DKD progression is accompanied by the loss of renal resident cells, followed by chronic inflammation and extracellular matrix deposition. Necroptosis is a newly discovered form of regulated cell death and is a major form of intrinsic cell loss in certain diabetic complications such as cardiomyopathy, intestinal disease, and retinal neuropathy; however, its significance in DKD is largely unknown...

ETHNOPHARMACOLOGICAL RELEVANCE: Diabetic nephropathy (DN) is one of the most common and serious complications of diabetes, which lacks effective treatment. Salviae Miltiorrhizae Radix Et Rhizoma is one of the key compatible traditional Chinese medicine in the prescription for the treatment of DN. Salvianolic acid B and tanshinone IIA are two monomer active components with high content and clear structure in Salvia miltiorrhiza, which can effectively improve early (DN), respectively. AIM OF THE STUDY: To evaluate the compatible effect of salvianolic acid B and tanshinone IIA on early DN rats and elucidate the mechanism...

Diabetic nephropathy (DN) is characterized by abnormal kidney energy metabolism, but its causes and contributions to DN pathogenesis are not clear. To examine this issue, we carried out targeted metabolomics profiling in a mouse model of DN that develops kidney disease resembling the human disorder. We found a distinct profile of increased lactate levels and impaired energy metabolism in kidneys of mice with DN, and treatment with an angiotensin-receptor blocker (ARB) reduced albuminuria, attenuated kidney pathology and corrected many metabolic abnormalities, restoring levels of lactate toward normal while increasing kidney ATP content...

INTRODUCTION: Diabetic nephropathy (DN) is the most common clinical complication of diabetes mellitus. Moringa isothiocyanate-1 (MIC-1) is effective in the treatment of diabetes mellitus, but its mechanism of action in DN remains obscure. This research specifically probed the role of MIC-1 in modulating renal injury in DN. METHODS: Six db/m mice were assigned to control group and twelve db/db mice were randomly allocated to the db/db and db/db + MIC-1 groups. The body and kidney weights of the mice were monitored...

RATIONALE: Renal hypoxia is one of the currently highlighted pathophysiologic mechanisms of diabetic nephropathy (DN). Both hypoxia-inducible factor-1α (HIF-1α) and HIF-2α are major regulators of renal adaptive responses to hypoxia. OBJECTIVES: This study aims to compare the effects of vildagliptin (a dipeptidyl peptidase-IV inhibitor, DPP-4i) and empagliflozin (a sodium-glucose cotransporter 2 inhibitor, SGLT2i) on the differential expression of renal HIF-1α/2α...

To investigate the intervention effect and mechanism of Zhenwu Decoction on diabetic nephropathy(DN) mice of spleen-kidney Yang deficiency syndrome based on the Rho-associated coiled-coil kinase(ROCK)/IκB kinase(IKK)/nuclear factor-κB(NF-κB) pathway. Ninety-five 7-week-old db/db male mice and 25 7-week-old db/m male mice were fed adaptively for one week. The DN model of spleen-kidney Yang deficiency syndrome was induced by Dahuang Decoction combined with hydrocortisone by gavage, and then the model was evaluated...

Diabetic kidney disease (DKD) is a leading cause of kidney failure. Previous studies demonstrated the therapeutic potential of Astragalus polysaccharide in treating diabetic nephropathy. Astragalus and Hongqi both come from the leguminous plant Astragalus, but their species and genera are different, belonging to the same family and different genera of traditional Chinese medicinal plants. However, the effects of Hedysarum polybotrys polysaccharide (HPS), a polysaccharide compound from Hongqi, on DKD, including its components and efficacy, have remained elusive...

BACKGROUNDS: Diabetes nephropathy (DN) is a growing public health concern worldwide. Renal dysfunction impairment in DN is intimately linked to ER stress and its related signaling pathways. Nonetheless, the underlying mechanism and biomarkers for this function of ER stress in the DN remain unknown. METHODS: Microarray datasets were retrieved from the Gene Expression Omnibus (GEO) database, and ER stress-related genes (ERSRGs) were downloaded from the MSigDB and GeneCards database...

Many studies have highlighted the importance of moderate exercise. While it can attenuate diabetic kidney disease, its mechanism has remained unclear. The level of myokine irisin in plasma increases during exercise. We found that irisin was decreased in diabetic patients and was closely related to renal function, proteinuria, and podocyte autophagy injury. Muscle-specific overexpression of PGC-1α (mPGC-1α) in a mouse model is known to increase plasma irisin levels. The mPGC-1α mice were crossed with db/m mice to obtain db/db mPGC-1α+ mice in the present study...

Diabetic nephropathy (DN), as the one of most common complications of diabetes, is generally diagnosed based on a longstanding duration, albuminuria, and decreased kidney function. Some patients with the comorbidities of diabetes and other primary renal diseases have similar clinical features to DN, which is defined as non-diabetic renal disease (NDRD). It is necessary to distinguish between DN and NDRD, considering they differ in their pathological characteristics, treatment regimes, and prognosis. Renal biopsy provides a gold standard; however, it is difficult for this to be conducted in all patients...