Erythropoietin protects lipopolysaccharide-induced renal mesangial cells from autophagy

Bi, Lingyun; Hou, Ruanling; Da-sheng, Yang; Li, Shujun; Zhao, Dean

doi:10.3892/etm.2014.2124

Cited by 11 publications

(7 citation statements)

References 24 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…However, the type of renal intrinsic cells involved in the alteration of autophagy as well as the alterations that occur in the autophagic pathway must be further investigated for autophagy-based intervention strategies in the future. Some studies on mesangial cells not only showed that high glucose induced the accumulation of p62, but also showed a reduction in autophagy-related gene expression of patients with DKD, suggesting that autophagic activity was inhibited in mesangial cells in DKD 34,35 . In addition, our previous study showed that the autophagic activity was severely inhibited, and increased expression of LC3 and the accumulation of p62 were found in the renal tubular epithelial cells in DKD 28 .…”

Section: Discussionmentioning

confidence: 99%

Lysosome restoration to activate podocyte autophagy: a new therapeutic strategy for diabetic kidney disease

et al. 2019

View full text Add to dashboard Cite

Autophagy, the intracellular lysosomal degradation process plays a pivotal role in podocyte homeostasis in diabetic kidney disease (DKD). Lysosomal function, autophagic activity, and their actions were investigated in vitro and in vivo. We found that LC3-II- and p62-positive vacuoles accumulated in podocytes of patients with DKD. Moreover, we found that advanced glycation end products (AGEs) could increase the protein expression of LC3-II and p62 in a dose- and time-dependent manner in cultured podocytes. However, the mRNA expression of LC3B, Beclin-1 or ATG7, as well as the protein level of Beclin-1 or ATG7 did not change significantly in the AGE-treated cells compared with that in control groups, suggesting that AGEs did not induce autophagy. In addition, AGEs led to an increase in the number of autophagosomes but not autolysosomes, accompanied with a failure in lysosomal turnover of LC3-II or p62, indicating that the degradation of autophagic vacuoles was blocked. Furthermore, we observed a dramatic decrease in the enzymatic activities, and the degradation of DQ-ovalbumin was significantly suppressed after podocytes were treated with AGEs. Plasma-irregular lysosomal-associated membrane protein 1 granules accompanied with the diffusion of cathepsin D expression and acridine orange redistribution were observed in AGE-treated podocytes, indicating that the lysosomal membrane permeability was triggered. Interestingly, we also found that AGEs-induced autophagic inhibition and podocyte injury were mimicked by the specific lysosomotropic agent, l-leucyl-l-leucine methyl ester. The exacerbated apoptosis and Rac-1-dependent actin-cytoskeletal disorganization were alleviated by an improvement in the lysosomal-dependent autophagic pathway by resveratrol plus vitamin E treatment in AGE-treated podocytes. However, the rescued effects were reversed by the addition of leupeptin, a lysosomal inhibitor. It suggests that restoring lysosomal function to activate autophagy may contribute to the development of new therapeutic strategies for DKD.

show abstract

Section: Discussionmentioning

confidence: 99%

Lysosome restoration to activate podocyte autophagy: a new therapeutic strategy for diabetic kidney disease

et al. 2019

View full text Add to dashboard Cite

show abstract

“…Although there is evidence that EPO/EpoR signaling protects tissue against ischemia and hypoxia through suppression of apoptosis (34), there is limited, and in fact controversial, information about the effect of EPO/EpoR signaling on autophagy (5,6,41,57,95). In an experimental model of neonatal necrotizing enterocolitis, EPO reduced both excessive autophagy and apoptosis (95), suppressed hyperoxia-induced autophagy, and contained cell damage (5).…”

Section: Discussionmentioning

confidence: 99%

Effects of erythropoietin receptor activity on angiogenesis, tubular injury, and fibrosis in acute kidney injury: a “U-shaped” relationship

Shi

Flores

et al. 2018

American Journal of Physiology-Renal Physiology

View full text Add to dashboard Cite

The erythropoietin receptor (EpoR) is widely expressed but its renoprotective action is unexplored. To examine the role of EpoR in vivo in the kidney, we induced acute kidney injury (AKI) by ischemia-reperfusion in mice with different EpoR bioactivities in the kidney. EpoR bioactivity was reduced by knockin of wild-type human EpoR, which is hypofunctional relative to murine EpoR, and a renal tubule-specific EpoR knockout. These mice had lower EPO/EpoR activity and lower autophagy flux in renal tubules. Upon AKI induction, they exhibited worse renal function and structural damage, more apoptosis at the acute stage (<7 days), and slower recovery with more tubulointerstitial fibrosis at the subacute stage (14 days). In contrast, mice with hyperactive EpoR signaling from knockin of a constitutively active human EpoR had higher autophagic flux, milder kidney damage, and better renal function at the acute stage but, surprisingly, worse tubulointerstitial fibrosis and renal function at the subacute stage. Either excess or deficient EpoR activity in the kidney was associated with abnormal peritubular capillaries and tubular hypoxia, creating a "U-shaped" relationship. The direct effects of EpoR on tubular cells were confirmed in vitro by a hydrogen peroxide model using primary cultured proximal tubule cells with different EpoR activities. In summary, normal erythropoietin (EPO)/EpoR signaling in renal tubules provides defense against renal tubular injury maintains the autophagy-apoptosis balance and peritubular capillary integrity. High and low EPO/EpoR bioactivities both lead to vascular defect, and high EpoR activity overides the tubular protective effects in AKI recovery.

show abstract

“…Suppression of excess autophagy could alleviate both acute cardiac injury and promote survival of recipient rats in a LPS-induced cardiomyocyte contractile dysfunction model [9]. Moreover, a study by Bi et al [10] reported that induction of autophagy promoted death of rat renal glomerular mesangial cells, while in hepatocytes, pretreatment with wortmannin could alleviate lipopolysaccharide/D-galactosamine-induced acute hepatocytotoxity and reduce apoptosis and necrosis through inhibition of autophagy [11]. These results indicate that induction of excessive autophagy may be harmful and could aggravate injury to organs.…”

Section: Introductionmentioning

confidence: 99%

The Role of Probiotics in Lipopolysaccharide-Induced Autophagy in Intestinal Epithelial Cells

Han

Zhang

Shi

et al. 2016

Cell Physiol Biochem

View full text Add to dashboard Cite

Background/Aims: Dysfunction of autophagy has been associated with loss of intestinal homeostasis. Lipopolysaccharide (LPS) from Gram-negative bacteria is known to be a major initiator of intestinal epithelial cell (IEC) autophagy. Although probiotics have been recognized to be involved in many therapeutic properties and participate in host defense responses, the molecular mechanisms by which probiotics exert these positive effects remain unknown. This study assessed the effect of probiotics on LPS-induced physical barrier dysfunction and the underlying mechanism of probiotic action in IECs with a focus on autophagy. Methods: A LPS-induced autophagic model was established in rat IEC18 cells wherein cells were treated with culture medium supernatants of Bifidobacteria following LPS intervention at indicated times. Autophagosomes in IEC18 cells were visualized by confocal microscopy after transfection with a tandem GFP-mCherry-LC3 construct and also by transmission electron microscopy. Autophagy-associated protein levels were analyzed by western blot and transepithelial electrical resistance (TEER) was measured using an epithelial voltohmmeter. Results: Probiotic treatment could effectively inhibit LPS-induced autophagy, as evidenced by the decreased ratio of microtubule-associated light chain 3 (LC3)-II/LC3-I, fewer autophagic vacuoles, and reduced punctate distribution of GFP-mCherry-LC3. In addition, probiotics prevented chloroquine (CQ) inhibition of autophagic flux and autophagolysosomal fusion as indicated by a failure to recruit LAMP1 and cathepsin D to lysosomes. Interestingly, ATG16L1 knockdown did not inhibit the effect of probiotics on LPS-induced autophagy. Furthermore, the diminished barrier function could be prevented by probiotics. Conclusions: We provide evidence that autophagy mediation by probiotics may be involved in enteroprotection against LPS-induced intestinal epithelial toxicity, and could serve as a novel mechanism through which probiotics promote and maintain gut homeostasis.

show abstract

Erythropoietin protects lipopolysaccharide-induced renal mesangial cells from autophagy

Cited by 11 publications

References 24 publications

Lysosome restoration to activate podocyte autophagy: a new therapeutic strategy for diabetic kidney disease

Lysosome restoration to activate podocyte autophagy: a new therapeutic strategy for diabetic kidney disease

Effects of erythropoietin receptor activity on angiogenesis, tubular injury, and fibrosis in acute kidney injury: a “U-shaped” relationship

The Role of Probiotics in Lipopolysaccharide-Induced Autophagy in Intestinal Epithelial Cells

Contact Info

Product

Resources

About