Activation of the angiotensin II receptor promotes autophagy in renal proximal tubular cells and affords protection from ischemia/reperfusion injury

Sugawara, Hirohito; Moniwa, Norihito; Kuno, Atsushi; Ohwada, Wataru; Osanami, Arata; Shibata, Satoru; Kimura, Yoshinobu; Abe, Koki; Gocho, Yufu; Tanno, Masaya; Miura, Tetsuji

doi:10.1016/j.jphs.2020.12.001

Cited by 12 publications

(8 citation statements)

References 48 publications

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“…All specimens were examined for morphological parameters, including epithelial cell vacuolization, tubular cell flattening, degeneration, tubular dilatation, hyaline cast, and debris materials in tubular lumen on a semi-quantitative score from 1 to 5, while the score of zero was assigned to the normal tissue without damage. 24 …”

Section: Methodsmentioning

confidence: 99%

Soluble Programmed Cell Death Protein 1 and Its Ligand: Potential Biomarkers to Predict Acute Kidney Injury After Surgery in Critically Ill Patients

Wang¹,

Zheng²,

Jiang³

et al. 2022

JIR

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Purpose Programmed cell death protein 1 (PD-1) and programmed death-ligand 1 (PD-L1) have been detected in injury kidney. However, their expressions are unclear in mice kidneys under renal ischemia-reperfusion injury (IRI). In this study, we would observe the expressions of PD-1 and PD-L1 in kidney tissues and analyze the association between the concentrations of PD-1 and PD-L1 in mouse kidney homogenate and the corresponding concentrations of soluble PD-1 (sPD-1) and soluble PD-L1 (sPD-L1) in plasma after renal IRI. Further, we explored the predictive value of sPD-1 and sPD-L1 for acute kidney injury (AKI) in high-risk patients after surgery. Methods This study established an AKI model induced by IRI in mice. Plasma, kidney samples, and homogenate were collected 0h, 24h, and 48h after surgery for immunohistochemistry and enzyme-linked immunosorbent assay. Then, we continuously enrolled 88 AKI high-risk patients who underwent noncardiac surgery. The biomarkers, including sPD-1, sPD-L1, and urine neutrophil gelatinase-associated lipocalin (NGAL), tissue inhibitor of metalloproteinase-2 (TIMP-2), insulin-like growth factor-binding protein 7 (IGFBP7), were detected immediately after surgery. Results Our data revealed the concentrations of PD-1 and PD-L1 in kidney homogenate, and sPD-1 and sPD-L1 in plasma significantly increased at 0h, 24h, and 48h after IRI. A positive association was found between PD-1 and sPD-1 ( r = 0.774, p < 0.001), and between PD-L1 and sPD-L1 ( r = 0.881, p < 0.001). Compared to NGAL, [TIMP-2]*[IGFBP7], sPD-1 and sPD-L1 showed better predictive abilities for AKI with an area under the ROC curve of 0.856 (95% confidence interval [CI]: 0.825–0.958, p < 0.001) and 0.906 (95% CI: 0.764–0.921, p < 0.001). Conclusion The increased expressions of PD-1 and PD-L1 in kidneys under IRI suggested they may play essential roles in AKI development. sPD-1 and sPD-L1 can indirectly reflect the expressions of PD-1 and PD-L1 in kidneys, respectively. sPD-1 and sPD-L1 showed excellent predictive ability for AKI in high-risk patients.

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Section: Methodsmentioning

confidence: 99%

Soluble Programmed Cell Death Protein 1 and Its Ligand: Potential Biomarkers to Predict Acute Kidney Injury After Surgery in Critically Ill Patients

Wang¹,

Zheng²,

Jiang³

et al. 2022

JIR

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“…Unlike podocytes, proximal tubular cells exhibit very low basal levels of autophagy under normal conditions [ 131 ]. However, autophagy in proximal tubular cells is increased in stress conditions, such as those caused by acute kidney injury consequent to ischemia and nephrotoxic agents, such as cisplatin [ 132 – 134 ]. Additionally, activation of autophagy in proximal tubular cells was suggested to be renoprotective to manage with both acute and chronic nephrotoxic stresses [ 134 ].…”

Section: Autophagy In Diabetic Nephropathymentioning

confidence: 99%

“…However, autophagy in proximal tubular cells is increased in stress conditions, such as those caused by acute kidney injury consequent to ischemia and nephrotoxic agents, such as cisplatin [ 132 – 134 ]. Additionally, activation of autophagy in proximal tubular cells was suggested to be renoprotective to manage with both acute and chronic nephrotoxic stresses [ 134 ]. Deficiency of autophagy in proximal tubular cells after deletion of Atg5 gene led to proteinuria and subsequent tubulointerstitial lesions [ 133 ].…”

Section: Autophagy In Diabetic Nephropathymentioning

confidence: 99%

Programmed Cell Death in Diabetic Nephropathy: A Review of Apoptosis, Autophagy, and Necroptosis

Erekat

2022

Med Sci Monit

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Diabetic nephropathy is a common complication of type I and type II diabetes, in which renal glomeruli are destroyed, resulting in renal damage, proteinuria, and hypertension. Apoptosis, autophagy, and necroptosis are 3 forms of programmed cell death that have been implicated in the pathogenesis of diabetic nephropathy. Apoptosis of podocytes leads to glomerular injury and podocyte depletion, which are associated with proteinuria and glomerular structural damage in diabetic nephropathy. Additionally, epithelial cells in the proximal convoluted tubules also undergo apoptosis in diabetic nephropathy, leading to tubular atrophy, which causes tubular cell depletion and the subsequent formation of atubular glomeruli in association with the loss of renal function. On the other hand, insufficiency of autophagy has been correlated with the pathogenesis of diabetic nephropathy. For instance, decreased autophagic activity has been shown in podocytes of the diabetic kidney, causing variations in podocyte function and subsequent disruption to the glomerular filtration barrier. Furthermore, attenuated autophagic activity has also been demonstrated in proximal tubular cells of the diabetic kidney, resulting in the buildup of impaired molecules and organelles, which are normally broken down by autophagy, leading to proteinuria. Moreover, necroptosis might have a key role in podocyte damage and subsequent decline in diabetic nephropathy. Thus, this article aims to review the mechanisms and effects of programmed cell death in diabetic nephropathy, including the roles of apoptosis, autophagy, and necroptosis.

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“…Autophagy keeps the cellular function of renal proximal tubule cells from RIRI-induced damage and nephrotoxic drugs [ 61 ]. Autophagy precedes apoptosis in proximal tubular cells, and its deficiency exacerbates cellular injury induced by RIRI [ 61 , 62 ]. Zhang et al reported that autophagy can be renoprotective via cell survival mechanisms involving several autophagy and apoptosis-related genes in the RIRI model [ 63 ].…”

Section: The Renal View Of Conventional Ras In Aki Induced By Ririmentioning

confidence: 99%

“…Zhang et al reported that autophagy can be renoprotective via cell survival mechanisms involving several autophagy and apoptosis-related genes in the RIRI model [ 63 ]. In the kidney, autophagy is regulated by the RAS; AT 1 R promotes autophagy in renal proximal tubular cells and increases renal tolerance to RIRI, thereby protecting the kidneys against RIR [ 62 ]. Telmisartan, an AT 1 R antagonist, has shown a renoprotective effect in RIRI; telmisartan pretreatment significantly decreased blood urea nitrogen (BUN) and serum creatinine (Cr) levels, inhibited the depletion of the antioxidant factors, and decreased lipid peroxidation induced by RIRI in the kidney [ 43 ].…”

Section: The Renal View Of Conventional Ras In Aki Induced By Ririmentioning

confidence: 99%

View of the Renin-Angiotensin System in Acute Kidney Injury Induced by Renal Ischemia-Reperfusion Injury

Karimi¹,

Maleki

Nematbakhsh

2022

J Renin Angiotensin Aldosterone Syst

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Renal ischemia-reperfusion injury (RIRI) is a sequence of complicated events that is defined as a reduction of the blood supply followed by reperfusion. RIRI is the leading cause of acute kidney injury (AKI). Among the diverse mediators that take part in RIRI-induced AKI, the renin-angiotensin system (RAS) plays an important role via conventional (angiotensinogen, renin, angiotensin-converting enzyme (ACE), angiotensin (Ang) II, and Ang II type 1 receptor (AT1R)) and nonconventional (ACE2, Ang 1-7, Ang 1-9, AT2 receptor (AT2R), and Mas receptor (MasR)) axes. RIRI alters the balance of both axes so that RAS can affect RIRI-induced AKI. In overall, the alteration of Ang II/AT1R and AKI by RIRI is important to consider. This review has looked for the effects and interactions of RAS activities during RIRI conditions.

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Activation of the angiotensin II receptor promotes autophagy in renal proximal tubular cells and affords protection from ischemia/reperfusion injury

Cited by 12 publications

References 48 publications

Soluble Programmed Cell Death Protein 1 and Its Ligand: Potential Biomarkers to Predict Acute Kidney Injury After Surgery in Critically Ill Patients

Soluble Programmed Cell Death Protein 1 and Its Ligand: Potential Biomarkers to Predict Acute Kidney Injury After Surgery in Critically Ill Patients

Programmed Cell Death in Diabetic Nephropathy: A Review of Apoptosis, Autophagy, and Necroptosis

View of the Renin-Angiotensin System in Acute Kidney Injury Induced by Renal Ischemia-Reperfusion Injury

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