VEGF-modified human embryonic mesenchymal stem cell implantation enhances protection against cisplatin-induced acute kidney injury

2011 ◽  
Vol 300 (1) ◽  
pp. F207-F218 ◽  
Author(s):  
Li Yuan ◽  
Min-Juan Wu ◽  
Hong-Yu Sun ◽  
Jun Xiong ◽  
Yi Zhang ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Acute Kidney Injury ◽  
Renal Function ◽  
Kidney Injury ◽  
Capillary Density ◽  
Tubular Structure ◽  
Protective Effects ◽  
Cell Protection ◽  
Nude Mouse Model ◽  
Renal Tubular

The implantation of mesenchymal stem cells (MSC) has been reported as a new technique to restore renal tubular structure and improve renal function in acute kidney injury (AKI). Vascular endothelial growth factor (VEGF) plays an important role in the renoprotective function of MSC. Whether upregulation of VEGF by a combination of MSC and VEGF gene transfer could enhance the protective effect of MSC in AKI is not clear. We investigated the effects of VEGF-modified human embryonic MSC (VEGF-hMSC) in healing cisplatin-injured renal tubular epithelial cells (TCMK-1) with a coculture system. We found that TCMK-1 viability declined 3 days after cisplatin pretreatment and that coculture with VEGF-hMSC enhanced cell protection via mitogenic and antiapoptotic actions. In addition, administration of VEGF-hMSC in a nude mouse model of cisplatin-induced kidney injury offered better protective effects on renal function, tubular structure, and survival as represented by increased cell proliferation, decreased cellular apoptosis, and improved peritubular capillary density. These data suggest that VEGF-modified hMSC implantation could provide advanced benefits in the protection against AKI by increasing antiapoptosis effects and improving microcirculation and cell proliferation.

Hesperidin Shows Protective Effects on Renal Function in Ischemia-induced Acute Kidney Injury (Sprague-Dawley Rats)

2019 ◽  
Vol 51 (8) ◽  
pp. 2838-2841
Author(s):  
Won Seo Park ◽  
Min Su Park ◽  
Sang Wook Kang ◽  
Seul A. Jin ◽  
Youngchul Jeon ◽  
...  
Keyword(s):  
Acute Kidney Injury ◽  
Renal Function ◽  
Kidney Injury ◽  
Protective Effects ◽  
Sprague Dawley ◽  
Sprague Dawley Rats

scholarly journals Renal tubular injury exacerbated by vasohibin-1 deficiency in a murine cisplatin-induced acute kidney injury model

2019 ◽  
Vol 317 (2) ◽  
pp. F264-F274 ◽  
Author(s):  
Satoshi Tanimura ◽  
Katsuyuki Tanabe ◽  
Hiromasa Miyake ◽  
Kana Masuda ◽  
Keigo Tsushida ◽  
...  
Keyword(s):  
Acute Kidney Injury ◽  
Endothelial Cells ◽  
Kidney Injury ◽  
Protective Effects ◽  
Tubular Injury ◽  
Injury Model ◽  
Peritubular Capillaries ◽  
Renal Tubular ◽  
And Function ◽  
Hospital Acquired

Acute kidney injury (AKI) is frequently encountered in clinical practice, particularly secondarily to cardiovascular surgery and administration of nephrotoxic agents, and is increasingly recognized for initiating a transition to chronic kidney disease. Clarifying the pathogenesis of AKI could facilitate the development of novel preventive strategies, because the occurrence of hospital-acquired AKI is often anticipated. Vasohibin-1 (VASH1) was initially identified as an antiangiogenic factor derived from endothelial cells. VASH1 expression in endothelial cells has subsequently been reported to enhance cellular stress tolerance. Considering the importance of maintaining peritubular capillaries in preventing the progression of AKI, the present study aimed to examine whether VASH1 deletion is involved in the pathogenesis of cisplatin-induced AKI. For this, we injected male C57BL/6J wild-type (WT) and VASH1 heterozygous knockout (VASH1+/−) mice intraperitoneally with either 20 mg/kg cisplatin or vehicle solution. Seventy-two hours after cisplatin injection, increased serum creatinine concentrations and renal tubular injury accompanied by apoptosis and oxidative stress were more prominent in VASH1+/− mice than in WT mice. Cisplatin-induced peritubular capillary loss was also accelerated by VASH1 deficiency. Moreover, the increased expression of ICAM-1 in the peritubular capillaries of cisplatin-treated VASH1+/− mice was associated with a more marked infiltration of macrophages into the kidney. Taken together, VASH1 expression could have protective effects on cisplatin-induced AKI probably by maintaining the number and function of peritubular capillaries.

scholarly journals Citrate shows protective effects on cardiovascular and renal function in ischemia-induced acute kidney injury

2017 ◽  
Vol 18 (1) ◽  
Author(s):  
Anja Bienholz ◽  
Jonas Reis ◽  
Pinar Sanli ◽  
Herbert de Groot ◽  
Frank Petrat ◽  
...  
Keyword(s):  
Acute Kidney Injury ◽  
Renal Function ◽  
Kidney Injury ◽  
Protective Effects

Hypoxia-inducible factor prolyl hydroxylase inhibitor roxadustat (FG-4592) protects against cisplatin-induced acute kidney injury

2018 ◽  
Vol 132 (7) ◽  
pp. 825-838 ◽  
Author(s):  
Yunwen Yang ◽  
Xiaowen Yu ◽  
Yue Zhang ◽  
Guixia Ding ◽  
Chunhua Zhu ◽  
...  
Keyword(s):  
Acute Kidney Injury ◽  
Renal Function ◽  
Target Genes ◽  
Periodic Acid ◽  
Kidney Injury ◽  
Protective Effects ◽  
Low Oxygen ◽  
Periodic Acid Schiff ◽  
Tubular Cells ◽  
Kidney Morphology

Renal hypoxia occurs in acute kidney injury (AKI) of various etiologies. Activation of hypoxia-inducible transcription factor (HIF) has been identified as an important mechanism of cellular adaptation to low oxygen. Preconditional HIF activation protects against AKI, suggesting a new approach in AKI treatment. HIF is degraded under normoxic conditions mediated by oxygen-dependent hydroxylation of specific prolyl residues of the regulative α-subunits by HIF prolyl hydroxylases (PHD). FG-4592 is a novel, orally active, small-molecule HIF PHD inhibitor for the treatment of anemia in patients with chronic kidney disease (CKD). The current study aimed to evaluate the effect of FG-4592 (Roxadustat) on cis-diamminedichloroplatinum (cisplatin)-induced kidney injury. In mice, pretreatment with FG-4592 markedly ameliorated cisplatin-induced kidney injury as shown by the improved renal function (blood urea nitrogen (BUN), serum creatinine (Scr), and cystatin C) and kidney morphology (periodic acid-Schiff (PAS) staining) in line with a robust blockade of renal tubular injury markers of kidney injury molecule 1 (KIM-1) and neutrophil gelatinase-associated lipocalin (NGAL). Meanwhile, the renal apoptosis and inflammation induced by cisplatin were also strikingly attenuated in FG-4592-treated mice. Along with the protective effects shown above, FG-4592 pretreatment strongly enhanced HIF-1α in tubular cells, as well as the expressions of HIF target genes. FG-4592 alone did not affect the renal function and morphology in mice. In vitro, FG-4592 treatment significantly up-regulated HIF-1α and protected the tubular cells against cisplatin-induced apoptosis. In summary, FG-4592 treatment remarkably ameliorated the cisplatin-induced kidney injury possibly through the stabilization of HIF. Thus, besides the role in treating CKD anemia, the clinical use of FG-4592 also could be extended to AKI.

scholarly journals p53 Deacetylation Alleviates Sepsis-Induced Acute Kidney Injury by Promoting Autophagy

2021 ◽  
Vol 12 ◽  
Author(s):  
Maomao Sun ◽  
Jiaxin Li ◽  
Liangfeng Mao ◽  
Jie Wu ◽  
Zhiya Deng ◽  
...  
Keyword(s):  
Acute Kidney Injury ◽  
P53 Protein ◽  
Cecal Ligation ◽  
Kidney Injury ◽  
Sirtuin 1 ◽  
Mechanistic Study ◽  
Tubular Damage ◽  
Protective Effects ◽  
Barrier Dysfunction ◽  
Renal Tubular

Recent studies have shown that autophagy upregulation can attenuate sepsis-induced acute kidney injury (SAKI). The tumor suppressor p53 has emerged as an autophagy regulator in various forms of acute kidney injury (AKI). Our previous studies showed that p53 acetylation exacerbated hemorrhagic shock-induced AKI and lipopolysaccharide (LPS)-induced endothelial barrier dysfunction. However, the role of p53-regulated autophagy in SAKI has not been examined and requires clarification. In this study, we observed the dynamic changes of autophagy in renal tubular epithelial cells (RTECs) and verified the protective effects of autophagy activation on SAKI. We also examined the changes in the protein expression, intracellular distribution (nuclear and cytoplasmic), and acetylation/deacetylation levels of p53 during SAKI following cecal ligation and puncture (CLP) or LPS treatment in mice and in a LPS-challenged human RTEC cell line (HK-2 cells). After sepsis stimulation, the autophagy levels of RTECs increased temporarily, followed by a sharp decrease. Autophagy inhibition was accompanied by an increased renal tubular injury score. By contrast, autophagy agonists could reduce renal tubular damage following sepsis. Surprisingly, the expression of p53 protein in both the renal cortex and HK-2 cells did not significantly change following sepsis stimulation. However, the translocation of p53 from the nucleus to the cytoplasm increased, and the acetylation of p53 was enhanced. In the mechanistic study, we found that the induction of p53 deacetylation, due to either the resveratrol/quercetin -induced activation of the deacetylase Sirtuin 1 (Sirt1) or the mutation of the acetylated lysine site in p53, promoted RTEC autophagy and alleviated SAKI. In addition, we found that acetylated p53 was easier to bind with Beclin1 and accelerated its ubiquitination-mediated degradation. Our study underscores the importance of deacetylated p53-mediated RTEC autophagy in future SAKI treatments.

scholarly journals Catechins: Therapeutic Perspectives in COVID-19-Associated Acute Kidney Injury

Molecules ◽  
2021 ◽  
Vol 26 (19) ◽  
pp. 5951
Author(s):  
Lúcio Ricardo Leite Diniz ◽  
Hatem A. Elshabrawy ◽  
Marilia Trindade de Santana Souza ◽  
Allana Brunna Sucupira Duarte ◽  
Sabarno Datta ◽  
...  
Keyword(s):  
Acute Kidney Injury ◽  
Renal Function ◽  
Strong Association ◽  
Kidney Injury ◽  
Protective Effects ◽  
Substantial Evidence ◽  
Pharmacological Activities ◽  
Renal Disorder ◽  
Organ Failures ◽  
Hospital Deaths

Data obtained from several intensive care units around the world have provided substantial evidence of the strong association between impairment of the renal function and in-hospital deaths of critically ill COVID-19 patients, especially those with comorbidities and requiring renal replacement therapy (RRT). Acute kidney injury (AKI) is a common renal disorder of various etiologies characterized by a sudden and sustained decrease of renal function. Studies have shown that 5–46% of COVID-19 patients develop AKI during hospital stay, and the mortality of those patients may reach up to 100% depending on various factors, such as organ failures and RRT requirement. Catechins are natural products that have multiple pharmacological activities, including anti-coronavirus and reno-protective activities against kidney injury induced by nephrotoxic agents, obstructive nephropathies and AKI accompanying metabolic and cardiovascular disorders. Therefore, in this review, we discuss the anti-SARS-CoV-2 and reno-protective effects of catechins from a mechanistic perspective. We believe that catechins may serve as promising therapeutics in COVID-19-associated AKI due to their well-recognized anti-SARS-CoV-2, and antioxidant and anti-inflammatory properties that mediate their reno-protective activities.

Sign in / Sign up

Export Citation Format

Share Document