Autophagy protects podocytes from sublytic complement induced injury

Lv, Qianying; Yang, Fulun; Chen, Kun

doi:10.1016/j.yexcr.2016.02.009

Cited by 21 publications

(16 citation statements)

References 22 publications

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“…The two processes may be triggered by common upstream signals, resulting in combined autophagy and apoptosis. In some cellular settings, autophagy can serve as a cell survival pathway, suppressing apoptosis [27]. Indeed, in the present study, rapamycin was found to decrease the apoptosis and concurrently improved the autophagy of podocytes induced by IgAN.…”

Section: Discussionsupporting

confidence: 55%

Rapamycin Induces Autophagy and Reduces the Apoptosis of Podocytes Under a Stimulated Condition of Immunoglobulin A Nephropathy

Liang¹,

Jin²,

Lin³

et al. 2017

Kidney Blood Press Res

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Backgroud/Aims: The aim of this study was to investigate the potential renoprotective effect of rapamycin on the autophagy of podocytes treated with the supernatant of mesangial cells cultured with aggregated IgA1 (aIgA1) from immunoglobulin A nephropathy (IgAN) patients. Methods: Monomeric IgA1 (mIgA1) was isolated from the serum of IgAN patients or healthy volunteers, and then transformed to aIgA1 by heating. Subsequently, the aIgA1-mesangial cell supernatant was prepared by collecting the medium of mouse mesangial cells (MSC1097) cultured with aIgA1 (100 mg/L) from different IgAN patients or healthy volunteers for 48 h. Subsequently mouse podocytes (MPC5) were exposed to the supernatant of the aIgA1-mesangial cells for 24 h, using 100 mg/L aIgA1 from healthy volunteers as the control group or 100 mg/L aIgA1 from IgAN patients as the IgANs group, in RPMI 1640 medium. The MPC5 cells in the IgANs+Rap group were cultured with rapamycin (10 nmol/L) and the supernatant of MSC-1097 cells cultured with aIgA1 from IgAN patients in RPMI 1640 medium. Autophagy was assessed by western blot analysis (LC3, p62), electron microscopy, and immunofluorescence staining (LC3, p62, and CD63). The apoptosis of podocytes was evaluated by flow cytometry, and the expression of apoptosis-associated proteins cleaved-caspase-3 and caspase-3 were determined by western blot analysis. Results: Deficient autophagy, which was evident by decreased LC3-II and CD63 levels, caused accumulation of p62, and fewer autophagosomes were observed in the MPC5 cells cultured with the IgAN supernatant, along with stronger expression of cleaved caspase-3 and a higher apoptosis rate. Inhibition of autophagy was alleviated in the IgANs+Rap group. The LC3-II/LC3-I ratio increased by almost 30%, the accumulated p62 amount was reduced by 50%, and the number of autophagosomes per podocyte increased to about 7 times that of the IgAN groups. These results were confirmed by immunofluorescence staining. In addition, the apoptosis rate of MPC5 cells decreased from 19.88% in the IgAN group to 16.78% in the IgANs+Rap group, which was accompanied by a weaker expression level of cleaved caspase-3. Conclusions: Rapamycin can reduce the apoptosis of podocytes by inducing autophagy in IgAN.

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Section: Discussionsupporting

confidence: 55%

Rapamycin Induces Autophagy and Reduces the Apoptosis of Podocytes Under a Stimulated Condition of Immunoglobulin A Nephropathy

Liang¹,

Jin²,

Lin³

et al. 2017

Kidney Blood Press Res

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“…Cells were analyzed on a CyAn ADP analyzer (Beckman Coulter, Inc.). FlowJo version 7.6 software (Tree Star, Inc., Ashland, OR, USA) was used to analyze the data ( 38 ).…”

Section: Methodsmentioning

confidence: 99%

Hepatic recruitment of CD11b+Ly6C+ inflammatory monocytes promotes hepatic ischemia/reperfusion injury

Song

Zhang

et al. 2017

Int J Mol Med

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Monocytes infiltrate damaged liver tissue during noninfectious liver injury and often have dual roles, perpetuating inflammation and promoting resolution of inflammation and fibrosis. However, how monocyte subsets distribute and are differentially recruited in the liver remain unclear. In the current study, the subpopulations of infiltrating monocytes were examined following liver ischemia/reperfusion (I/R) injury in mice using flow cytometry. CD11b+Ly6C high (Ly6Chi) cells (inflammatory monocytes) and CD11b+Ly6C low cells (reparative monocytes) were recruited into the liver following I/R injury. Treatment with clodronate-loaded liposomes, which transiently deplete systemic macrophages, alleviated hepatic damage. Mice genetically deficient in C-C motif chemokine ligand 2 (CCL2), or its receptor C-C chemokine receptor 2 (CCR2), exhibited diminished hepatic damage compared with wild-type mice following I/R, by controlling intrahepatic inflammatory Ly6Chi monocyte accumulation. In addition, the CCR2 specific inhibitor RS504393 alleviated hepatic I/R injury. The results suggest that the CCR2/ CCL2 axis an important role in monocyte infiltration and may represent a novel target for the treatment of liver I/R injury.

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“…Rat GMC culture and sublytic C5b-9 determination were described in our previous studies (5,9). Rabbit Thy-1 Ab and NHS (providing heterologous complement) were used to assemble C5b-9 on rat GMC membrane to avoid homologous restriction factors (e.g., CD59, which could disrupt C5b-9 formation on GMC membranes) (40). Of note, 5% Thy-1 Ab and 4% NHS were used in our study, with ,0.5% lactate dehydrogenase release regarded as a sublytic effect.…”

Section: Gmc Culture and Sublytic C5b-9 Determinationmentioning

confidence: 99%

Sublytic C5b-9 Induces IL-23 and IL-36a Production by Glomerular Mesangial Cells via PCAF-Mediated KLF4 Acetylation in Rat Thy-1 Nephritis

Zhang

Xie

et al. 2018

The Journal of Immunology

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Sublytic C5b-9 formation on glomerular mesangial cells in rat Thy-1 nephritis (Thy-1N), a model of human mesangioproliferative glomerulonephritis, is accompanied by the production of proinflammatory cytokines, but the relationship between sublytic C5b-9 and cytokine synthesis and the underlying mechanism remains unclear. To explore the problems mentioned above, in this study, we first examined the levels of proinflammatory ILs (e.g., IL-23 and IL-36a) as well as transcription factor (KLF4) and coactivator (PCAF) in the renal tissues of Thy-1N rats and in the glomerular mesangial cell line (HBZY-1) stimulated by sublytic C5b-9. Then, we further determined the role of KLF4 and PCAF in sublytic C5b-9–induced IL-23 and IL-36a production as well as the related mechanism. Our results showed that the levels of KLF4, PCAF, IL-23, and IL-36a were obviously elevated. Mechanistic investigation revealed that sublytic C5b-9 stimulation could increase IL-23 and IL-36a synthesis through KLF4 and PCAF upregulation, and KLF4 and PCAF could form a complex, binding to the IL-23 or IL-36a promoter in a KLF4-dependent manner, causing gene transcription. Importantly, KLF4 acetylation by PCAF contributed to sublytic C5b-9–induced IL-23 and IL-36a transcription. Besides, the KLF4 binding regions on IL-23 or IL-36a promoters and the KLF4 lysine site acetylated by PCAF were identified. Furthermore, silencing renal KLF4 or PCAF gene could significantly inhibit IL-23 or IL-36a secretion and tissue damage of Thy-1N rats. Collectively, these findings implicate that the KLF4/PCAF interaction and KLF4 acetylation by PCAF play a pivotal role in the sublytic C5b-9–mediated IL-23 and IL-36a production of Thy-1N rats.

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Autophagy protects podocytes from sublytic complement induced injury

Cited by 21 publications

References 22 publications

Rapamycin Induces Autophagy and Reduces the Apoptosis of Podocytes Under a Stimulated Condition of Immunoglobulin A Nephropathy

Rapamycin Induces Autophagy and Reduces the Apoptosis of Podocytes Under a Stimulated Condition of Immunoglobulin A Nephropathy

Hepatic recruitment of CD11b+Ly6C+ inflammatory monocytes promotes hepatic ischemia/reperfusion injury

Sublytic C5b-9 Induces IL-23 and IL-36a Production by Glomerular Mesangial Cells via PCAF-Mediated KLF4 Acetylation in Rat Thy-1 Nephritis

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