Angiopoietin 1 influences ischemic reperfusion renal injury via modulating endothelium survival and regeneration

Abstract

Background Damage to the endothelium due to ischemia reperfusion injury (IRI) leads to a disruption of the microvasculature, which could be influenced by angiopoietin 1 via its effects on endothelium. We investigated the physiological and therapeutic roles of angiopoietin 1 in renal IRI using angiopoietin 1 knockout and over-expression mice. Methods Renal IRI was induced by clamping the right renal artery seven days after left uninephrectomy for 25 min followed by reperfusion. A whole body angiopoietin 1 knockout was achieved by induction with tamoxifen. The renal tubule over-expression of angiopoietin 1 was induced by doxycycline. Results In the normal mice, the renal expression of angiopoietin 1 increased 7 days to 14 days after IRI. The angiopoietin 1 knockout caused a delay in the recovery of renal function, less tubular regeneration and more residual tubular necrosis. The endothelial density was lower and the VE-cadherin protein loss was greater in the knockout mice. The over-expression of angiopoietin 1 attenuated the tubular necrosis and renal function impairment 1 and 3 days after IRI. The loss of the endothelium was ameliorated in the over-expression mice. This protective effect was associated with the up-regulation of the gene expression of epidermal growth factor , hepatocyte growth factor, and insulin like growth factor-1 and less tubular apoptosis. The over-expression of angiopoietin 1 stimulated tumor necrosis factor-α , C-C chemokine receptor type 2 and CX3C chemokine receptor 1 inflammatory gene expression, but did not influence macrophage infiltration. Conclusions Altogether, the augmentation and downregulation of angiopoietin 1 attenuated renal damage and impaired renal recovery, respectively, by influencing the survival/regeneration of the endothelium. The manipulation of angiopoietin 1 represents a novel therapeutic approach for the treatment of ischemic kidney injury. Electronic supplementary material The online version of this article (10.1186/s10020-019-0072-7) contains supplementary material, which is available to authorized users.

Erythropoietin Derived Peptide Improved Endoplasmic Reticulum Stress and Ischemia-Reperfusion Related Cellular and Renal Injury

“…Renal ischemia-reperfusion (IR) injury is inevitable in kidney transplantation, which greatly affects the survival of allograft (1)(2)(3). IR injury also often occurs in native kidneys subjected to a variety of causes such as cardiovascular surgery, dehydration, and sepsis.…”

“…The underlying mechanisms of IR injury and repair are complicated including endoplasmic reticulum stress (ERS), mitochondria dysfunction, cell death, and inflammation (7)(8)(9)(10). Improving ERS and TEC apoptosis have been considered to be effective methods to alleviate renal IR injury (3,11).…”

Acute kidney injuries induced by thrombotic microangiopathy following severe hemorrhage in puerperants: A case series and literature review

“…As a result of the severe postpartum hemorrhage, the patients required the transfusion of a large amount of red blood cells, plasma, and resuscitation uid. This could potentially have caused an ischemia-reperfusion injury in renal epithelial cells [23,24], further promoting the alternative complement pathway activation, and the ampli cation of the complement-mediated injury [25,26]. The dysregulation of the alternative complement pathway may induce TMA [27].…”

Mesangial Cells and Glomerular Endothelial Cells Crosstalk in Rat Anti-Thy-1 Nephritis through VEGFA/VEGFAR2 and Angpt2/Tie2 pathway

“…In this study, the addition of Angpt1 to the coculture system increased Tie2 phosphorylation and inhibited cell proliferation, but Angpt2 expression was not affected. Studies have shown that Angpt1 can reduce the risk of acute kidney injury (AKI) in critically ill patients [49] and can promote renal recovery by enhancing EC, suggesting that Angpt1 is a potential AKI treatment [50]. Studies have also shown that injecting COMP-Angpt1 (synthetically modi ed Angpt1) into db/db mice can reduce proteinuria and alleviate mesangial expansion and GBM thickening, indicating that Angpt1 is also bene cial in DN [51].…”