Id1 expression in kidney endothelial cells protects against diabetes‐induced microvascular injury

Abstract

The inhibitor of differentiation (Id) transcription regulators, which are induced in response to oxidative stress, promote cell proliferation and inhibit senescence. Inhibitor of differentiation 1 (Id1) expression is limited to endothelial cells (EC) in the normal mouse kidney and is required for a normal response to injury. Endothelial dysfunction leads to the development of diabetic nephropathy, and so, we hypothesized that endothelial Id1 may help protect against hyperglycemia‐induced microvascular injury and nephropathy. Here, we tested this hypothesis by using streptozotocin to induce diabetes in Id1 knockout (KO) mice and WT B6;129 littermates and examining the mice at 3 months. Expression of Id1 was observed to be increased 15‐fold in WT kidney EC, and Id1 KO mice exhibited increased mesangial and myofibroblast proliferation, matrix deposition, and albuminuria compared with WT mice. Electron microscopy demonstrated peritubular capillary EC injury and lumen narrowing, and fluorescence microangiography showed a 45% reduction in capillary perfusion area with no reduction in CD31‐stained areas in Id1 KO mice. Microarray analysis of EC isolated from WT and KO control and diabetic mice demonstrated activation of senescence pathways in KO cells. Kidneys from KO diabetic mice showed increased histological expression of senescence markers. In addition, premature senescence in cultured KO EC was also seen in response to oxidative stress. In conclusion, endothelial Id1 upregulation with hyperglycemia protects against microvascular injury and senescence and subsequent nephropathy.

The crosstalk between glomerular endothelial cells and podocytes controls their responses to metabolic stimuli in diabetic nephropathy

“…Both ID1 and ID3 were upregulated by high glucose in cultured human pancreatic islets or insulinoma cells 78 . Furthermore, the expression of ID1 has been shown to increase markedly in a streptozotocin model of diabetes and ID1 knockout in this model exhibited accelerated pathological alterations in the kidneys 79 . Less is known at present about the specific role of ID3 in the context of diabetic nephropathy, but our findings suggest that it may also play an important role in its pathogenesis.…”

Melatonin Maintains Homeostasis and Potentiates the Anti-inflammatory Response in Staphylococcus aureus-Induced Mastitis through microRNA-16b/YAP1

“…ID1, TNF-α, IL8, IL2, PGLYRP1, PTX3, AMPK, and TGB-β1 are all closely related to inflammatory cytokines and cellular immunity. To investigate the therapeutic effects of melatonin on staphylococcal mastitis, we measured the mRNA expression of inflammation-related genes.…”

“…These results show that melatonin maintains homeostasis and potentiates the antiinflammatory response in vivo. ID1, 26 TNF-α, 27 IL8, 28 IL2, 29 PGLYRP1, 30 PTX3, 31 AMPK, 32 and TGB-β1 33 are all closely related to inflammatory cytokines and cellular immunity. To investigate the therapeutic effects of melatonin on staphylococcal mastitis, we measured the mRNA expression of inflammation-related genes.…”

The Effect of Allograft Inflammatory Factor-1 on Inflammation, Oxidative Stress, and Autophagy via miR-34a/ATG4B Pathway in Diabetic Kidney Disease

“…Furthermore, the pathogenic signals from GECs are transmitted into podocytes, as well as mesangial cells, and induce a phenotypic switch that modifies their intracellular signaling leading to dysfunction [51][52][53]. At the present, an increasing number of studies suggest that GECs dysfunction as a key event in the pathogenesis of DKD [54][55][56][57]. Thus, it is very important to elucidate the mechanism of GECs dysfunction induced by high glucose for the pathogenesis of diabetic nephropathy.…”