Revisiting Experimental Models of Diabetic Nephropathy

Abstract

Diabetes prevalence is constantly increasing and, nowadays, it affects more than 350 million people worldwide. Therefore, the prevalence of diabetic nephropathy (DN) has also increased, becoming the main cause of end-stage renal disease (ESRD) in the developed world. DN is characterized by albuminuria, a decline in glomerular filtration rate (GFR), hypertension, mesangial matrix expansion, glomerular basement membrane thickening, and tubulointerstitial fibrosis. The therapeutic advances in the last years have been able to modify and delay the natural course of diabetic kidney disease (DKD). Nevertheless, there is still an urgent need to characterize the pathways that are involved in DN, identify risk biomarkers and prevent kidney failure in diabetic patients. Rodent models provide valuable information regarding how DN is set and its progression through time. Despite the utility of these models, kidney disease progression depends on the diabetes induction method and susceptibility to diabetes of each experimental strain. The classical DN murine models (Streptozotocin-induced, Akita, or obese type 2 models) do not develop all of the typical DN features. For this reason, many models have been crossed to a susceptible genetic background. Knockout and transgenic strains have also been created to generate more robust models. In this review, we will focus on the description of the new DN rodent models and, additionally, we will provide an overview of the available methods for renal phenotyping.

Midkine: Utility as a Predictor of Early Diabetic Nephropathy in Children with Type 1 Diabetes Mellitus

“…It enhances both neutrophil and macrophage migration into the tubulointerstitial regions, which is detrimental to kidney health ( 7 ). Studies involving human biopsy specimens and animal models have reported that macrophage infiltration is a characteristic of DN, confirming the concept that inflammation plays a crucial role in the pathogenesis of DN ( 33 ).…”

FOXA1 Suppresses SATB1 Transcription and Inactivates the Wnt/β-Catenin Pathway to Alleviate Diabetic Nephropathy in a Mouse Model

“… 1 , 2 Like many renal diseases, DN is characterized by proteinuria, which is frequently induced by death and loss of podocytes, followed by reduced glomerular filtration, mesangial matrix expansion glomerulosclerosis and the consequent kidney failure. 3 , 4 Initiation and progression of DN is not always predictable and the DN development is a long-term process occurring gradually over many years. 5 Several mechanisms such as activation of the profibrotic transforming growth factor beta (TGF-β) signaling, 6 suppression in fibroblast growth factor receptor 1 signaling, 7 loss of endothelial glucocorticoid receptor, 8 and dysregulated central metabolism 9 have been reported to be associated with DN development.…”

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

“…The etiology of diabetic kidney disease is complicated and involved many factors, including genetic factors, hypertension, abnormalities of renal hemodynamics, as well as metabolism of vasoactive substances ( Lu et al, 2019 ). Diabetic nephropathy (DN), the major cause of chronic kidney disease, is characterized by albuminuria, lowered glomerular filtration rate, hypertension, and mesangial matrix expansion in addition to tubulointerstitial fibrosis ( Giralt-Lopez et al, 2020 ). The progression of DN has been suggested to attribute to various pathological mechanisms, including inflammation and fibrosis ( Calle and Hotter, 2020 ).…”