Diabetic nephropathy (DN) is the leading cause of end-stage renal disease globally. The primary initiating mechanism in DN is hyperglycemia-induced vascular dysfunction, but its progression is due to different pathological mechanisms, including oxidative stress, inflammatory cells infiltration, inflammation and fibrosis. Macrophages (Mφ) accumulation in kidneys correlates strongly with serum creatinine, interstitial myofibroblast accumulation and interstitial fibrosis scores. However, whether or not Mφ polarization is involved in the progression of DN has not been adequately defined. The prevalence of the different phenotypes during the course of DN, the existence of hybrid phenotypes and the plasticity of these cells depending of the environment have led to inconclusive results. In the same sense the role of the different macrophage phenotype in fibrosis associated or not to DN warrants additional investigation into Mφ polarization and its role in fibrosis. Due to the association between fibrosis and the progressive decline of renal function in DN, and the role of the different phenotypes of Mφ in fibrosis, in this review we examine the role of macrophage phenotype control in DN and highlight the potential factors contributing to phenotype change and injury or repair in DN.

/pdf/macrophage-phenotype-and-fibrosis-in-diabetic-nephropathy-4koti6xwh1.pdf

Macrophage Phenotype and Fibrosis in Diabetic Nephropathy.

Defining therapeutic targets for renal fibrosis: Exploiting the biology of pathogenesis.

http://www.cell.com/article/S1097276522001095/pdf

How the ends signal the end: Regulation by E3 ubiquitin ligases recognizing protein termini

Tectorigenin enhances PDX1 expression and protects pancreatic β-cells by activating ERK and reducing ER stress

Tectorigenin ameliorated high-fat diet-induced nonalcoholic fatty liver disease through anti-inflammation and modulating gut microbiota in mice.

Tectorigenin attenuates diabetic nephropathy by improving vascular endothelium dysfunction through activating AdipoR1/2 pathway.

Amelioration of hepatic steatosis by dietary essential amino acid-induced ubiquitination.

Parkinson’s disease (PD) is one of the most common neurodegenerative diseases and is pathologically characterized by α-synucleinopathy, which is harmful to dopaminergic neurons. However, the underlying mechanisms and pathogenesis of PD remain unclear. The AAA + ATPase Thorase was identified as being essential for neuroprotection and synaptic plasticity by regulating the AMPA receptor trafficking. Here, we found that conditional knockout of Thorase resulted in motor behaviors indicative of neurodegeneration. Genetic deletion of Thorase exacerbated phenotypes of α-synucleinopathy in a familial PD-like A53T mouse model, whereas overexpression of Thorase prevented α-syn accumulation in vivo. Biochemical and cell cultures studies presented here suggest that Thorase interacts with α-syn and regulates the degradation of ubiquitinated α-syn. Thorase deficiency promotes α-syn aggregation in primary cultured neurons. The discoveries in this study provide us with a further understanding of the pathogenesis of α-synucleinopathies including PD.

/pdf/atpase-thorase-deficiency-causes-a-synucleinopathy-and-1z3zva4r.pdf

Qi Yang

Papers

Tectorigenin attenuates diabetic nephropathy by improving vascular endothelium dysfunction through activating AdipoR1/2 pathway.

Amelioration of hepatic steatosis by dietary essential amino acid-induced ubiquitination.

ATPase Thorase Deficiency Causes α-Synucleinopathy and Parkinson’s Disease-like Behavior