Role of toll receptors in diabetic nephropathy

Abstract

Objectives: Diabetic nephropathy is the leading cause of chronic kidney disease. The pathogenesis of DN remains incompletely understood. It has been recently demonstrated that inflammatory processes play a significant role in the development and progression of DN. Toll-like receptors play a fundamental role in the innate immune system by triggering proinflammatory signaling pathways. Our aim is to evaluate the expression of TLRs on monocytes and relate their expression with inflammation in HD patients with & without diabetic nephropathy. Method: In a case control study (60) patients from Alkasr El Aini Hospital on hemodialysis were divided into two groups: Group 1, 30 patients on heamodialysis not due to diabetic nephropathy, Group 2, 30 patients on heamodialysis due to diabetic nephropathy, compared to Group 3, including 30 healthy controls. All participants were subjected to: Full medical history, complete physical examination, Serum creatinine, uric acid, A1C, fundus examination, detection of TLR2, TLR expression by real time PCR in peripheral blood mononuclear cells. Data were statically calculated using SPSS, comparision between groups was done using student T test comparing 2 groups, correlation using spearman's correlation. Results: Diabetic had significantly increased TLR2, TLR4 mRNA in peripheral blood mononuclear cells compared to controls and non diabetics patient on heamodialysis (p < 0.001), TLR2, TLR4 significantly correlated with dialysis duration in diabetic (p < 0.001), no correlation with A1C in relation to TLR2 (p = 0.078), TLR4 (p = 0.163). Conclusion: TLR2, TLR4 were significantly elevated in diabetic on dialysis initiating event in the patho-genesis of DN, providing a link between hyperglycemia and hypoxia with inflammation and fibrosis within the kidney. Hence, therapeutic interventions aimed at targeting the inflammatory component through interruption of TLR signaling may be a novel strategy to target prevention and treatment of DN.

Patterns of Toll-Like Receptor Expressions and Inflammatory Cytokine Levels and Their Implications in the Progress of Insulin Resistance and Diabetic Nephropathy in Type 2 Diabetic Patients

“… Lin et al (2012) showed increased expression of TLR4 in human proximal tubular epithelial cells under hyperglycaemic conditions, pointing toward a role of TLR4 in tubulointerstitial inflammation in DNP. Also, our results agreed with the study of Mansour et al (2014) , which concluded that the level of TLR2 and 4 is elevated in patients with end-stage DNP compared to that of patients with end-stage renal disease due to non-DNP. Badr et al (2019) found that TLRs were overexpressed in microvascular complicated type 2 diabetic patients as compared to non-complicated type 2 diabetic patients.…”

Efektivitas Ekstrak Etanol Biji Pinang Terhadap Densitas GLUT4 pada Sel-Sel Otot Rangka Mencit yang Terinduksi Hiperglikemia

“…Secara tragis, diabetes dapat mengakibatkan 4,9 juta kematian per tahun (IDF 2015). Hal ini disebabkan komplikasi diabetik meliputi neuropati, disfungsi erektil, nefropati, retinopati, makroangiopati seperti penyakit kardiovaskuler, stroke dan kaki diabetik (King et al 2016;Ramesh et al 2015;Mansour et al 2014;Djrolo et al 2014). Diabetes bahkan dapat dikaitkan dengan peningkatan mortalitas akibat timbulnya beberapa kanker seperti kanker payudara, kanker usus buntu (colorectal cancer) dan kanker prostat (Spangler & Kirk 2014).…”