Molecular Mechanisms in Early Diabetic Kidney Disease: Glomerular Endothelial Cell Dysfunction

Lassén, Emelie

doi:10.3390/ijms21249456

Cited by 77 publications

(63 citation statements)

References 173 publications

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“…Metabolic changes associated with DM, along with activation of the renin–angiotensin–aldosterone system (RAAS), cause the generation of ROS and AFAs (nitric oxide, nitrogen dioxide, and peroxynitrite) in GECs. Endothelin-1 (Edn1) activity in DM increases oxidative stress, which causes endothelial nitric oxide (NO) depletion and degradation of endothelial glycocalyx [ 243 ].…”

Section: Role Of Modified Albumin In Pathogenesis Of Diseasesmentioning

confidence: 99%

Serum Albumin in Health and Disease: Esterase, Antioxidant, Transporting and Signaling Properties

Belinskaia

Voronina

Шмурак

et al. 2021

IJMS

141

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Being one of the main proteins in the human body and many animal species, albumin plays a decisive role in the transport of various ions—electrically neutral and charged molecules—and in maintaining the colloidal osmotic pressure of the blood. Albumin is able to bind to almost all known drugs, as well as many nutraceuticals and toxic substances, largely determining their pharmaco- and toxicokinetics. Albumin of humans and respective representatives in cattle and rodents have their own structural features that determine species differences in functional properties. However, albumin is not only passive, but also an active participant of pharmacokinetic and toxicokinetic processes, possessing a number of enzymatic activities. Numerous experiments have shown esterase or pseudoesterase activity of albumin towards a number of endogeneous and exogeneous esters. Due to the free thiol group of Cys34, albumin can serve as a trap for reactive oxygen and nitrogen species, thus participating in redox processes. Glycated albumin makes a significant contribution to the pathogenesis of diabetes and other diseases. The interaction of albumin with blood cells, blood vessels and tissue cells outside the vascular bed is of great importance. Interactions with endothelial glycocalyx and vascular endothelial cells largely determine the integrative role of albumin. This review considers the esterase, antioxidant, transporting and signaling properties of albumin, as well as its structural and functional modifications and their significance in the pathogenesis of certain diseases.

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Section: Role Of Modified Albumin In Pathogenesis Of Diseasesmentioning

confidence: 99%

Serum Albumin in Health and Disease: Esterase, Antioxidant, Transporting and Signaling Properties

Belinskaia

Voronina

Шмурак

et al. 2021

IJMS

141

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“…Oxidative stress with increased production of reactive oxygen species and dysregulation of VEGF are pathogenic mechanisms in early diabetic nephropathy [ 18 , 19 ]. High levels of oxygen with HBOT might be expected to increase proteinuria, but we found the opposite.…”

Section: Discussionmentioning

confidence: 99%

“…General antioxidant approaches in diabetic nephropathy have failed in large trials [ 18 , 20 ]. This makes the finding of a possible proteinuria reducing effect of HBOT remarkable, as it may constitute a first description of an intervention on the redox systems that reduces proteinuria in patients.…”

Section: Discussionmentioning

confidence: 99%

Renal Effects of Hyperbaric Oxygen Therapy in Patients with Diabetes Mellitus: A Retrospective Study

Sedlacek

Harlan

Buckey

2021

International Journal of Nephrology

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Hyperbaric oxygen therapy (HBOT) is an adjunctive treatment for patients with diabetic foot ulcers. The prolonged high oxygen level used in HBOT can produce oxidative stress, which may be harmful to the kidney. Animal experiments suggest HBOT does not harm renal function and may have an antiproteinuric effect, but little is known on the effect of HBOT in humans. We performed a retrospective chart review of 94 patients with diabetes mellitus who underwent HBOT at our institution over an eight-year period. Thirty-two patients had serum creatinine levels within 60 days of the start and the end of treatment. Creatinine levels were 1.41 ± 0.89 mg/dl before and 1.52 ± 1.17 mg/dl after hyperbaric treatments with no statistically significant difference (mean (postcreatinine + precreatinine/2) = 0.10 mg/dl, SE = 0.11, t = 0.89). Twenty-three patients had proteinuria measurements before and after HBOT mainly by urine dipstick analysis. A Wilcoxon signed-rank test showed less proteinuria after HBOT than before (N = 23, p = 0.002 ). Proteinuria was absent in 7 of 23 patients (30%) before HBOT and 13 of 23 patients (57%) after HBOT, a reduction by almost 50%. This observation is remarkable because oxidative stress might be expected to increase rather than decrease proteinuria.

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“…In addition, activated podocytes have been shown to influence endothelial glycocalyx remodeling and loss in experimental FSGS and in vitro (Ebefors et al, 2019). In diabetic kidney disease, GEC dysfunction and glycocalyx damage represent initiating steps in diabetic albuminuria in humans and in experimental models (Zhao et al, 2006;Satchell and Tooke, 2008;Yuen et al, 2012;Dogne et al, 2016;Lassen and Daehn, 2020). Importantly, bidirectional signaling enables cells in the glomeruli to function effectively, where podocytes control GEC growth and survival via crosstalk of paracrine vascular endothelial growth factor alpha (VEGFA and VEGF-R; Sison et al, 2010;Jeansson et al, 2011).…”

Section: The Functional Barriermentioning

confidence: 99%

Section: The Functional Barriermentioning

confidence: 99%

Modeling the Glomerular Filtration Barrier and Intercellular Crosstalk

et al. 2021

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The glomerulus is a compact cluster of capillaries responsible for blood filtration and initiating urine production in the renal nephrons. A trilaminar structure in the capillary wall forms the glomerular filtration barrier (GFB), composed of glycocalyx-enriched and fenestrated endothelial cells adhering to the glomerular basement membrane and specialized visceral epithelial cells, podocytes, forming the outermost layer with a molecular slit diaphragm between their interdigitating foot processes. The unique dynamic and selective nature of blood filtration to produce urine requires the functionality of each of the GFB components, and hence, mimicking the glomerular filter in vitro has been challenging, though critical for various research applications and drug screening. Research efforts in the past few years have transformed our understanding of the structure and multifaceted roles of the cells and their intricate crosstalk in development and disease pathogenesis. In this review, we present a new wave of technologies that include glomerulus-on-a-chip, three-dimensional microfluidic models, and organoids all promising to improve our understanding of glomerular biology and to enable the development of GFB-targeted therapies. Here, we also outline the challenges and the opportunities of these emerging biomimetic systems that aim to recapitulate the complex glomerular filter, and the evolving perspectives on the sophisticated repertoire of cellular signaling that comprise the glomerular milieu.

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Molecular Mechanisms in Early Diabetic Kidney Disease: Glomerular Endothelial Cell Dysfunction

Cited by 77 publications

References 173 publications

Serum Albumin in Health and Disease: Esterase, Antioxidant, Transporting and Signaling Properties

Serum Albumin in Health and Disease: Esterase, Antioxidant, Transporting and Signaling Properties

Renal Effects of Hyperbaric Oxygen Therapy in Patients with Diabetes Mellitus: A Retrospective Study

Modeling the Glomerular Filtration Barrier and Intercellular Crosstalk

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