Verbascoside inhibits the epithelial‐mesenchymal transition of prostate cancer cells through high‐mobility group box 1/receptor for advanced glycation end‐products/ TGF ‐β pathway

2021 ◽  
Author(s):  
Chun‐Hsien Wu ◽  
Chung‐Hsien Chen ◽  
Pei‐Fang Hsieh ◽  
Yen‐Hsi Lee ◽  
Wade Wei‐Ting Kuo ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cancer Cells ◽  
Advanced Glycation End Products ◽  
Epithelial Mesenchymal Transition ◽  
High Mobility ◽  
Prostate Cancer Cells ◽  
Advanced Glycation ◽  
Mesenchymal Transition ◽  
Glycation End Products ◽  
End Products

scholarly journals 3H-1,2-Dithiole-3-Thione Protects Lens Epithelial Cells against Fructose-Induced Epithelial-Mesenchymal Transition via Activation of AMPK to Eliminate AKR1B1-Induced Oxidative Stress in Diabetes Mellitus

Antioxidants ◽  
2021 ◽  
Vol 10 (7) ◽  
pp. 1086
Author(s):  
Tsung-Tien Wu ◽  
Ying-Ying Chen ◽  
Chiu-Yi Ho ◽  
Tung-Chen Yeh ◽  
Gwo-Ching Sun ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Epithelial Cells ◽  
Advanced Glycation End Products ◽  
Epithelial Mesenchymal Transition ◽  
Human Lens ◽  
Lens Epithelial Cells ◽  
Advanced Glycation ◽  
Mesenchymal Transition ◽  
Glycation End Products ◽  
End Products

Studies demonstrated that the receptor of advanced glycation end products (RAGE) induced epithelial-mesenchymal transition (EMT) formation in the lens epithelial cells (LECs) of diabetic cataracts. This work investigated how 3H-1,2-dithiole-3-thione (D3T) reduces EMT formation in LECs of the fructose-induced diabetes mellitus (DM). LECs were isolated during cataract surgery from patients without DM or with DM. In a rat model, fructose (10% fructose, eight weeks) with or without D3T (10 mg/kg/day) treatment induced DM, as verified by blood pressure and serum parameter measurements. We observed that the formation of advanced glycation end products (AGEs) was significantly higher in epithelial human lens of DM (+) compared to DM (−) cataracts. Aldose reductase (AKR1B1), AcSOD2, and 3-NT were significantly enhanced in the rat lens epithelial sections of fructose-induced DM, however, the phosphorylation level of AMPKT172 showed a reversed result. Interestingly, administration of D3T reverses the fructose-induced effects in LECs. These results indicated that AMPKT172 may be required for reduced superoxide generation and the pathogenesis of diabetic cataract. Administration of D3T reverses the fructose-induced EMT formation the LECs of fructose-induced DM. These novel findings suggest that the D3T may be a candidate for the pharmacological prevention of cataracts in patients with DM.

Advanced glycation end-products associate with podocytopathy in type II diabetic patients

2021 ◽  
Author(s):  
Rajkishor Nishad ◽  
Tahaseen V Syed ◽  
Manga Motrapu ◽  
Rajesh Kavvuri ◽  
Kiranmayi Kodali ◽  
...  
Keyword(s):  
Kidney Disease ◽  
Kidney Function ◽  
Advanced Glycation End Products ◽  
Diabetic Patients ◽  
Type Ii ◽  
Advanced Glycation ◽  
Mesenchymal Transition ◽  
Glycation End Products ◽  
End Products ◽  
Carboxymethyl Lysine

Abstract Background The prevalence of diabetes reaches epidemic proportions, affecting the incidence of diabetic nephropathy (DN) and associated end-stage kidney disease (ESKD). Diabetes is the leading cause of ESKD since 30–40% of diabetic patients develop DN. Albuminuria and eGFR have been considered a surrogate outcome of chronic kidney disease, and the search for a biomarker that predicts progression to diabetic kidney disease is intense.Methods We analyzed the association of serum advanced glycation end-products (AGEs) index (AGI) with impaired kidney function in uncontrolled diabetic patients (type II, n = 130) with albuminuria ranging from (150 to 450 mg/day). The kidney biopsy specimens were also examined for the association of AGEs, particularly carboxymethyl lysine (CML) with kidney function. Further, we also assessed the effect of carboxymethyl lysine on glomerular injury and podocytopathy in experimental animals.Results We observed a strong correlation between AGI and impaired kidney function in miroalbuminuric patients with hyperglycemia. A significant association between CML levels and impaired kidney function was noticed. Administration of CML in mice showed heavy proteinuria and glomerular abnormalities. Reduced podocyte number observed in mice administered with CML could be attributed to the epithelial-mesenchymal transition (EMT) of podocytes. Conclusion Serum AGEs could be independently related to the podocyte injury vis-a-vis the risk of DN progression to ESKD in patients with microalbuminuria. AGEs or CML could be considered a prognostic marker to assess microalbuminuria progression to ESKD in diabetic patients.

scholarly journals High-mobility group box 1 inhibits HCO3− absorption in medullary thick ascending limb through a basolateral receptor for advanced glycation end products pathway

2015 ◽  
Vol 309 (8) ◽  
pp. F720-F730 ◽  
Author(s):  
David W. Good ◽  
Thampi George ◽  
Bruns A. Watts
Keyword(s):  
Advanced Glycation End Products ◽  
Basolateral Membrane ◽  
High Mobility ◽  
High Mobility Group ◽  
Renal Tubules ◽  
Thick Ascending Limb ◽  
Advanced Glycation ◽  
Medullary Thick Ascending Limb ◽  
Glycation End Products ◽  
End Products

High-mobility group box 1 (HMGB1) is a damage-associated molecule implicated in mediating kidney dysfunction in sepsis and sterile inflammatory disorders. HMGB1 is a nuclear protein released extracellularly in response to infection or injury, where it interacts with Toll-like receptor 4 (TLR4) and other receptors to mediate inflammation. Previously, we demonstrated that LPS inhibits HCO3- absorption in the medullary thick ascending limb (MTAL) through a basolateral TLR4-ERK pathway (Watts BA III, George T, Sherwood ER, Good DW. Am J Physiol Cell Physiol 301: C1296–C1306, 2011). Here, we examined whether HMGB1 could inhibit HCO3- absorption through the same pathway. Adding HMGB1 to the bath decreased HCO3− absorption by 24% in isolated, perfused rat and mouse MTALs. In contrast to LPS, inhibition by HMGB1 was preserved in MTALs from TLR4−/− mice and was unaffected by ERK inhibitors. Inhibition by HMGB1 was eliminated by the receptor for advanced glycation end products (RAGE) antagonist FPS-ZM1 and by neutralizing anti-RAGE antibody. Confocal immunofluorescence showed expression of RAGE in the basolateral membrane domain. Inhibition of HCO3−absorption by HMGB1 through RAGE was additive to inhibition by LPS through TLR4 and to inhibition by Gram-positive bacterial molecules through TLR2. Bath amiloride, which selectively prevents inhibition of MTAL HCO3− absorption mediated through Na+/H+ exchanger 1 (NHE1), eliminated inhibition by HMGB1. We conclude that HMGB1 inhibits MTAL HCO3− absorption through a RAGE-dependent pathway distinct from TLR4-mediated inhibition by LPS. These studies provide new evidence that HMGB1-RAGE signaling acts directly to impair the transport function of renal tubules. They reveal a novel paradigm for sepsis-induced renal tubule dysfunction, whereby exogenous pathogen-associated molecules and endogenous damage-associated molecules act directly and independently to inhibit MTAL HCO3− absorption through different receptor signaling pathways.

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