Age-related mitochondrial dysfunction as a key factor in COVID-19 disease

Experimental Gerontology, Journal Year: 2020, Volume and Issue: 142, P. 111147 - 111147

Published: Nov. 7, 2020

Language: Английский

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SGLT2 Inhibitor Empagliflozin and DPP4 Inhibitor Linagliptin Reactivate Glomerular Autophagy in db/db Mice, a Model of Type 2 Diabetes

International Journal of Molecular Sciences, Journal Year: 2020, Volume and Issue: 21(8), P. 2987 - 2987

Published: April 23, 2020

Recent data have indicated the emerging role of glomerular autophagy in diabetic kidney disease. We aimed to assess effect SGLT2 inhibitor empagliflozin, DPP4 linagliptin, and their combination, on a model type 2 diabetes. Eight-week-old male db/db mice were randomly assigned treatment with empagliflozin–linagliptin or vehicle for 8 weeks. Age-matched non-diabetic db/+ acted as controls. To estimate autophagy, immunohistochemistry beclin-1 LAMP-1 was performed. Podocyte assessed by counting volume density (Vv) autophagosomes, lysosomes autolysosomes transmission electron microscopy. LC3B LAMP-1, markers, caspase-3 Bcl-2, apoptotic evaluated renal cortex western blot. Vehicle-treated had weak staining reduced Vv podocytes. Empagliflozin both monotherapy enhanced areas increased autophagosomes Renal Bcl-2 restored actively treated animals. expression empagliflozin group; decreased group only. Mesangial expansion, podocyte foot process effacement urinary albumin excretion mitigated agents. The provide further explanation mechanism renoprotective inhibitors

Language: Английский

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Improving the residual risk of renal and cardiovascular outcomes in diabetic kidney disease: A review of pathophysiology, mechanisms, and evidence from recent trials

Diabetes Obesity and Metabolism, Journal Year: 2021, Volume and Issue: 24(3), P. 365 - 376

Published: Nov. 15, 2021

Based on global estimates, almost 10% of adults have diabetes, whom 40% are estimated to also chronic kidney disease (CKD). Almost 2 decades ago, treatments targeting the renin-angiotensin system (RAS) were shown slow progression disease. More recently, studies reported additive benefits antihyperglycaemic sodium-glucose co-transporter-2 inhibitors in combination with RAS both CKD and cardiovascular outcomes. However, these recent data showed that patients continue progress failure or die from kidney- cardiovascular-related causes. Therefore, new agents needed address this continuing risk. Overactivation mineralocorticoid (MR) receptor contributes inflammation fibrosis, suggesting it is an appropriate treatment target diabetes CKD. Novel, selective non-steroidal MR antagonists being studied patients, results two large recently completed clinical trials one such treatment, finerenone, significantly reduces events compared standard care. This review summarizes pathogenic mechanisms type examines potential benefit novel disease-modifying inflammatory fibrotic factors patients.

Language: Английский

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Glucose Variability: How Does It Work?

International Journal of Molecular Sciences, Journal Year: 2021, Volume and Issue: 22(15), P. 7783 - 7783

Published: July 21, 2021

A growing body of evidence points to the role glucose variability (GV) in development microvascular and macrovascular complications diabetes. In this review, we summarize data on GV-induced biochemical, cellular molecular events involved pathogenesis diabetic complications. Current indicate that deteriorating effect GV target organs can be realized through oxidative stress, glycation, chronic low-grade inflammation, endothelial dysfunction, platelet activation, impaired angiogenesis renal fibrosis. The effects dysfunction hypercoagulability could aggravated by hypoglycemia, associated with high GV. Oscillating hyperglycemia contributes beta cell which leads a further increase completes vicious circle. cells, cytotoxic includes mitochondrial endoplasmic reticulum stress disturbances autophagic flux, are accompanied reduced viability, activation apoptosis abnormalities proliferation. These up- down-regulation large number genes activity signaling pathways such as PI3K/Akt, NF-κB, MAPK (ERK), JNK TGF-β/Smad. Epigenetic modifications mediate postponed fluctuations. multiple deteriorative provide support for considering it therapeutic

Language: Английский

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Potential Therapeutic Targets for Cisplatin-Induced Kidney Injury: Lessons from Other Models of AKI and Fibrosis

Journal of the American Society of Nephrology, Journal Year: 2021, Volume and Issue: 32(7), P. 1559 - 1567

Published: May 28, 2021

The effectiveness of cisplatin, a mainstay in the treatment many solid organ cancers, is hindered by dose-limiting nephrotoxicity. Cisplatin causes AKI 30% patients. Patients who do not develop clinical standards during are still at risk for long-term decline kidney function and development CKD. connection between CKD has become increasingly studied, with renal fibrosis hallmark development. To prevent both short- effects researchers must use models that reflect types pathology. Although lot known about cisplatin-induced AKI, very little mechanisms which repeated low levels cisplatin lead to In this review, strategies used various rodent injury, its progression fibrosis, or both, examined gain mechanistic insights identify potential therapeutic targets pathologies. Reviewing results from these highlights diverse highly complex role cell death, senescence, endoplasmic reticulum stress, autophagy, immune activation acute chronic injuries. several injury needed agents will all aspects injury.

Language: Английский

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JAK/STAT pathway promotes the progression of diabetic kidney disease via autophagy in podocytes

European Journal of Pharmacology, Journal Year: 2021, Volume and Issue: 902, P. 174121 - 174121

Published: April 24, 2021

Language: Английский

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Programmed Cell Death in Diabetic Nephropathy: A Review of Apoptosis, Autophagy, and Necroptosis

Medical Science Monitor, Journal Year: 2022, Volume and Issue: 28

Published: Aug. 10, 2022

Diabetic nephropathy is a common complication of type I and II diabetes, in which renal glomeruli are destroyed, resulting damage, proteinuria, hypertension. Apoptosis, autophagy, necroptosis 3 forms programmed cell death that have been implicated the pathogenesis diabetic nephropathy. Apoptosis podocytes leads to glomerular injury podocyte depletion, associated with proteinuria structural damage Additionally, epithelial cells proximal convoluted tubules also undergo apoptosis nephropathy, leading tubular atrophy, causes depletion subsequent formation atubular association loss function. On other hand, insufficiency autophagy has correlated For instance, decreased autophagic activity shown kidney, causing variations function disruption filtration barrier. Furthermore, attenuated demonstrated buildup impaired molecules organelles, normally broken down by proteinuria. Moreover, might key role decline Thus, this article aims review mechanisms effects including roles apoptosis, necroptosis.

Language: Английский

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A Review of Traditional Chinese Medicine on Treatment of Diabetic Nephropathy and the Involved Mechanisms

The American Journal of Chinese Medicine, Journal Year: 2022, Volume and Issue: 50(07), P. 1739 - 1779

Published: Jan. 1, 2022

Diabetic nephropathy (DN) is a common microvascular complication of diabetes mellitus (DM), which can lead to renal failure in diabetic patients. At present, the first-line drugs for DN are mainly renin–angiotensin system (RAS) inhibitors or angiotensin receptor blockers, and latest approved aldosterone antagonist finerenone, delay progression end-stage disease (ESRD), but therapeutic effect still not ideal. With history thousands years, traditional Chinese medicine (TCM) has rich experience treatment DN. Based on theory TCM, clinical focuses generating fluid nourishing blood, Qi Yin, detoxifying detumescent. In recently effects mechanisms TCM prescription, herbal medicine, its active components have received extensive attention new drug development. This paper reviews research progress mechanism

Language: Английский

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Autophagy and its therapeutic potential in diabetic nephropathy

Frontiers in Endocrinology, Journal Year: 2023, Volume and Issue: 14

Published: March 20, 2023

Diabetic nephropathy (DN), the leading cause of end-stage renal disease, is most significant microvascular complication diabetes and poses a severe public health concern due to lack effective clinical treatments. Autophagy lysosomal process that degrades damaged proteins organelles preserve cellular homeostasis. Emerging studies have shown disorder in autophagy results accumulation diabetic cells promotes development DN. regulated by nutrient-sensing pathways including AMPK, mTOR, Sirt1, several intracellular stress signaling such as oxidative endoplasmic reticulum stress. An abnormal nutritional status excess stresses caused diabetes-related metabolic disorders disturb autophagic flux, dysfunction Here, we summarized role DN focusing on modulate therapeutic interferences

Language: Английский

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JAK/STAT3 signaling in cardiac fibrosis: a promising therapeutic target

Frontiers in Pharmacology, Journal Year: 2024, Volume and Issue: 15

Published: March 1, 2024

Cardiac fibrosis is a serious health problem because it common pathological change in almost all forms of cardiovascular diseases. characterized by the transdifferentiation cardiac fibroblasts (CFs) into myofibroblasts and excessive deposition extracellular matrix (ECM) components produced activated myofibroblasts, which leads to fibrotic scar formation subsequent dysfunction. However, there are currently few effective therapeutic strategies protecting against fibrogenesis. This lack largely molecular mechanisms remain unclear despite extensive research. The Janus kinase/signal transducer activator transcription (JAK/STAT) signaling cascade an extensively present intracellular signal transduction pathway can regulate wide range biological processes, including cell proliferation, migration, differentiation, apoptosis, immune response. Various upstream mediators such as cytokines, growth factors hormones initiate transmission via this play corresponding regulatory roles. STAT3 crucial player JAK/STAT its activation related inflammation, malignant tumors autoimmune illnesses. Recently, JAK/STAT3 has been spotlight for role occurrence development promote proliferation CFs production ECM proteins, thus leading fibrosis. In manuscript, we discuss structure, transactivation regulation review recent progress on Moreover, summarize current challenges opportunities targeting treatment summary, information presented article critical comprehending fibrosis, will also contribute future research aimed at anti-fibrotic signaling.

Language: Английский

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