Pathogenic Pathways and Therapeutic Approaches Targeting Inflammation in Diabetic Nephropathy

Abstract

Diabetic nephropathy (DN) is associated with an increased morbidity and mortality, resulting in elevated cost for public health systems. DN is the main cause of chronic kidney disease (CKD) and its incidence increases the number of patients that develop the end-stage renal disease (ESRD). There are growing epidemiological and preclinical evidence about the close relationship between inflammatory response and the occurrence and progression of DN. Several anti-inflammatory strategies targeting specific inflammatory mediators (cell adhesion molecules, chemokines and cytokines) and intracellular signaling pathways have shown beneficial effects in experimental models of DN, decreasing proteinuria and renal lesions. A number of inflammatory molecules have been shown useful to identify diabetic patients at high risk of developing renal complications. In this review, we focus on the key role of inflammation in the genesis and progression of DN, with a special interest in effector molecules and activated intracellular pathways leading to renal damage, as well as a comprehensive update of new therapeutic strategies targeting inflammation to prevent and/or retard renal injury.

Oxidative Stress Markers in Chronic Kidney Disease with Emphasis on Diabetic Nephropathy

“…The primary pathological mechanism that links oxidative stress, inflammation, and CKD progression includes an initial injury to the kidney by intra- and extracellular oxygen-derived radicals and the resultant inflammation [ 98 ]. In recent years, some important review papers have been published showing the importance of inflammation in the pathogenesis and progression of CKD [ 16 , 20 , 23 , 43 , 99 , 100 , 101 , 102 , 103 ]. More details about the role of inflammation in CKD is beyond the scope of this review.…”

Magnoflorine Ameliorates Inflammation and Fibrosis in Rats With Diabetic Nephropathy by Mediating the Stability of Lysine-Specific Demethylase 3A

“…The progression of DN has been suggested to attribute to various pathological mechanisms, including inflammation and fibrosis ( Calle and Hotter, 2020 ). The current therapeutic maneuver of diabetic patients focuses on glycemic control and antihypertensive/lipidlowering treatments; however, these involvements do not prevent the development of chronic kidney disease in most diabetic patients ( Rayego-Mateos et al, 2020 ). Therefore, the development for novel therapeutic approaches against DN is an area of great importance.…”

Anti-inflammatory, antioxidant and renoprotective effects of SOCS1 mimetic peptide in the BTBR ob/ob mouse model of type 2 diabetes

“…30 31 The participation of JAK/STAT signaling in the development and progression of DN has been validated as one of the main ways of eliciting the production of cytokines, chemokines, interferons, transcription and growth factors by kidney cells, and therefore responsible for maintaining the local proinflammatory state in the diabetic kidney. [32][33][34] Transcriptomic analysis in human DN revealed a direct relationship between tubulointerstitial JAK1, JAK2 and JAK3 (mainly JAK2), STAT1-3 gene expression, and the progression of kidney failure. 35 Our findings suggest an upregulation and compartmental activation of STAT1/3 in BTBR ob/ob diabetic kidneys, and a compensatory increase of SOCS1/3 proteins, which is in line with our previous findings in kidney biopsies of patients with T2D and experimental models.…”