scholarly journals Connexin 43: A Target for the Treatment of Inflammation in Secondary Complications of the Kidney and Eye in Diabetes

2022 ◽  
Vol 23 (2) ◽  
pp. 600
Author(s):  
Chelsy L. Cliff ◽  
Bethany M. Williams ◽  
Christos E. Chadjichristos ◽  
Ulrik Mouritzen ◽  
Paul E. Squires ◽  
...  
Keyword(s):  
Connexin 43 ◽  
Sterile Inflammation ◽  
Receptor Protein ◽  
Secondary Complications ◽  
Danger Signals ◽  
Membrane Bound ◽  
Models Of Disease ◽  
Stage Renal Disease ◽  
End Stage ◽  
And Function

Of increasing prevalence, diabetes is characterised by elevated blood glucose and chronic inflammation that precedes the onset of multiple secondary complications, including those of the kidney and the eye. As the leading cause of end stage renal disease and blindness in the working population, more than ever is there a demand to develop clinical interventions which can both delay and prevent disease progression. Connexins are membrane bound proteins that can form pores (hemichannels) in the cell membrane. Gated by cellular stress and injury, they open under pathophysiological conditions and in doing so release ‘danger signals’ including adenosine triphosphate into the extracellular environment. Linked to sterile inflammation via activation of the nod-like receptor protein 3 inflammasome, targeting aberrant hemichannel activity and the release of these danger signals has met with favourable outcomes in multiple models of disease, including secondary complications of diabetes. In this review, we provide a comprehensive update on those studies which document a role for aberrant connexin hemichannel activity in the pathogenesis of both diabetic eye and kidney disease, ahead of evaluating the efficacy of blocking connexin-43 specific hemichannels in these target tissues on tissue health and function.

scholarly journals Renoprotective Effects of DPP-4 Inhibitors

Antioxidants ◽  
2021 ◽  
Vol 10 (2) ◽  
pp. 246
Author(s):  
Daiji Kawanami ◽  
Yuichi Takashi ◽  
Hiroyuki Takahashi ◽  
Ryoko Motonaga ◽  
Makito Tanabe
Keyword(s):  
Diabetic Kidney Disease ◽  
Experimental Studies ◽  
Review Article ◽  
Glucose Lowering ◽  
Beneficial Effects ◽  
Glucose Levels ◽  
Membrane Bound ◽  
Stage Renal Disease ◽  
End Stage

Diabetic kidney disease (DKD) is the leading cause of end-stage renal disease (ESRD) worldwide. Dipeptidyl peptidase (DPP)-4 inhibitors are widely used in the treatment of patients with type 2 diabetes (T2D). DPP-4 inhibitors reduce glucose levels by inhibiting degradation of incretins. DPP-4 is a ubiquitous protein with exopeptidase activity that exists in cell membrane-bound and soluble forms. It has been shown that an increased renal DPP-4 activity is associated with the development of DKD. A series of clinical and experimental studies showed that DPP-4 inhibitors have beneficial effects on DKD, independent of their glucose-lowering abilities, which are mediated by anti-fibrotic, anti-inflammatory, and anti-oxidative stress properties. In this review article, we highlight the current understanding of the clinical efficacy and the mechanisms underlying renoprotection by DPP-4 inhibitors under diabetic conditions.

scholarly journals Lysophosphatidic Acid Signaling in Diabetic Nephropathy

2019 ◽  
Vol 20 (11) ◽  
pp. 2850 ◽  
Author(s):  
Jong Lee ◽  
Donghee Kim ◽  
Yoon Oh ◽  
Hee-Sook Jun
Keyword(s):  
Diabetic Nephropathy ◽  
Signaling Pathways ◽  
Lysophosphatidic Acid ◽  
Kidney Diseases ◽  
Cell Damage ◽  
Cell Structure ◽  
Research Findings ◽  
Stage Renal Disease ◽  
End Stage ◽  
And Function

Lysophosphatidic acid (LPA) is a bioactive phospholipid present in most tissues and body fluids. LPA acts through specific LPA receptors (LPAR1 to LPAR6) coupled with G protein. LPA binds to receptors and activates multiple cellular signaling pathways, subsequently exerting various biological functions, such as cell proliferation, migration, and apoptosis. LPA also induces cell damage through complex overlapping pathways, including the generation of reactive oxygen species, inflammatory cytokines, and fibrosis. Several reports indicate that the LPA–LPAR axis plays an important role in various diseases, including kidney disease, lung fibrosis, and cancer. Diabetic nephropathy (DN) is one of the most common diabetic complications and the main risk factor for chronic kidney diseases, which mostly progress to end-stage renal disease. There is also growing evidence indicating that the LPA–LPAR axis also plays an important role in inducing pathological alterations of cell structure and function in the kidneys. In this review, we will discuss key mediators or signaling pathways activated by LPA and summarize recent research findings associated with DN.

scholarly journals Podocytes—The Most Vulnerable Renal Cells in Preeclampsia

2020 ◽  
Vol 21 (14) ◽  
pp. 5051
Author(s):  
Ewa Kwiatkowska ◽  
Katarzyna Stefańska ◽  
Maciej Zieliński ◽  
Justyna Sakowska ◽  
Martyna Jankowiak ◽  
...  
Keyword(s):  
Current Knowledge ◽  
Damage Mechanism ◽  
Endothelial Damage ◽  
Main Role ◽  
Long Time ◽  
National Cohort ◽  
History Of ◽  
Stage Renal Disease ◽  
End Stage ◽  
And Function

Preeclampsia (PE) is a disorder that affects 3–5% of normal pregnancies. It was believed for a long time that the kidney, similarly to all vessels in the whole system, only sustained endothelial damage. The current knowledge gives rise to a presumption that the main role in the development of proteinuria is played by damage to the podocytes and their slit diaphragm. The podocyte damage mechanism in preeclampsia is connected to free VEGF and nitric oxide (NO) deficiency, and an increased concentration of endothelin-1 and oxidative stress. From national cohort studies, we know that women who had preeclampsia in at least one pregnancy carried five times the risk of developing end-stage renal disease (ESRD) when compared to women with physiological pregnancies. The focal segmental glomerulosclerosis (FSGS) is the dominant histopathological lesion in women with a history of PE. The kidney’s podocytes are not subject to replacement or proliferation. Podocyte depletion exceeding 20% resulted in FSGS, which is a reason for the later development of ESRD. In this review, we present the mechanism of kidney (especially podocytes) injury in preeclampsia. We try to explain how this damage affects further changes in the morphology and function of the kidneys after pregnancy.

Nocturnal hemodialysis is associated with restoration of impaired endothelial progenitor cell biology in end-stage renal disease

2005 ◽  
Vol 289 (4) ◽  
pp. F679-F684 ◽  
Author(s):  
Christopher T. Chan ◽  
Shu Hong Li ◽  
Subodh Verma
Keyword(s):  
Renal Disease ◽  
High Power ◽  
End Stage Renal Disease ◽  
High Power Field ◽  
Endothelial Progenitor ◽  
Nocturnal Hemodialysis ◽  
Stage Renal Disease ◽  
End Stage ◽  
And Function ◽  
Esrd Patients

Cardiovascular disease is the principal cause of death in end-stage renal disease (ESRD) patients. Endothelial progenitor cells (EPCs) play a critical role in vascular repair, and improving EPC biology represents a novel therapeutic target. Three groups of age- and gender-matched patients were studied: 1) 10 healthy control, 2) 12 conventional hemodialysis (CHD) patients, and 3) 10 nocturnal hemodialysis (NHD) patients. EPC number and migratory function were assessed. Left ventricular mass index (LVMI) was derived, and correlations between EPC biology, uremic clearance, and LVMI were made. Compared with controls, EPC number and function were markedly impaired in CHD patients [(3.48 ± 1.2 vs. 0.86 ± 0.20%/50,000 cells, P < 0.05) and (18.8 ± 2.64 vs. 3.75 ± 0.34 cells/high-power field, P < 0.05), respectively]. In contrast, EPC number and function were normal in NHD patients [(3.48 ± 1.17 vs. 3.83 ± 0.77%/50,000 cells) and (18.8 ± 2.6 vs. 22.2 ± 2.4 cells/high-power field), respectively]. Among ESRD patients, EPC number and function inversely correlated with predialysis urea concentration ( r = −0.40; r = −0.57), LVMI ( r = −0.41; −0.46) and systolic BP ( r = −0.58; r = −0.44). We demonstrate that NHD is associated with restoration of abnormal EPC biology in ESRD. Given the increasing importance of EPCs in the repair and restoration of cardiovascular function, these data have important clinical implications for vascular risk in ESRD patients.

Sign in / Sign up

Export Citation Format

Share Document