Rapamycin Enhances Repressed Autophagy and Attenuates Aggressive Progression in a Rat Model of IgA Nephropathy

Liu, Di; Liu, Yexin; Chen, Guochun; He, Liyu; Tang, Chengyuan; Wang, Chang; Yang, Darong; Li, Huiqiong; Dong, Zheng; Liu, Hong

doi:10.1159/000456039

Cited by 27 publications

(29 citation statements)

References 43 publications

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“…Previous studies have revealed that TG has therapeutic effects against various nephropathies, including IgA nephropathy, diabetic nephropathy and membranous nephropathy. Treatment with the autophagy activator rapamycin has been reported to reduce the progression of proteinuria and alleviate pathological lesions in IgA nephropathy rats ( 10 ).…”

Section: Discussionmentioning

confidence: 99%

Tripterygium glycoside protects against puromycin amino nucleoside‑induced podocyte injury by upregulating autophagy

et al. 2018

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Abstract. Tripterygium glycoside (TG), an active ingredient of the widely used chinese herb Tripterygium wilfordii Hook F, has immunosuppressive and anti-inflammatory effects. Previous studies have indicated that TG is a potentially effective therapeutic option to treat nephrotic syndrome. The mechanism underlying the therapeutic effect of TG, including its effect on autophagy and apoptosis in podocyte injury, remains to be fully elucidated. The present study aimed to assess the protective effect of TG on podocytes via its potential role in the activation of autophagic and phosphatidylinositol 3-kinase (PI3K) pathways. Using flow cytometry, western blot analysis, cell counting kit-8 assays and transmission electron microscopy analysis, the effects of TG on puromycin aminonucleoside (PAN)-induced podocyte injury were investigated. chloroquine (cQ), an inhibitor of autophagy, was used to assess the importance of autophagy in the protective effect of TG. In addition, LY294002, an inhibitor of class III PI3K, was used to identify which signaling pathways TG is involved in. PAN caused marked apoptosis of podocytes, which was significantly antagonized by TG. The expression of microtubule-associated protein 1A/1B-light chain 3 and the appearance of autophagosomes increased significantly following TG treatment, whereas the expression levels of p62 and cleaved caspase-3 were markedly decreased. Podocyte apoptosis decreased significantly when the podocytes were treated with TG compared with the levels of apoptosis in the PAN-and PAN+cQ-treated groups. The expression of phosphorylated AKT was increased significantly in the TG-treated groups, and the effects of TG on the podocytes were significantly inhibited by LY294002. In conclusion, TG protected podocytes from PAN-induced injury, and the effects were attributable to the activation of autophagy, mainly via a PI3K-dependent pathway.

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Section: Discussionmentioning

confidence: 99%

Tripterygium glycoside protects against puromycin amino nucleoside‑induced podocyte injury by upregulating autophagy

et al. 2018

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“…(3) Moreover, extensive researches have found that coagulation is related to in ammatory response, and IgAN is also an in ammatory disease. IgAN patients are commonly associated with alteration of various in ammatory cytokines [50], which may be related to the activation of procoagulant factors and renal brosis [51,52]. In addition, there are some limitations to our study.…”

Section: Discussionmentioning

confidence: 93%

Coagulation parameters are associated with the prognosis of immunoglobulin A nephropathy: a retrospective study

Xia

Liu

Peng

et al. 2020

Preprint

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Background. Interstitial fibrosis/tubular atrophy (T) score is a known determinant of the progression of immunoglobulin A nephropathy (IgAN). Strong evidence indicates that the components of the coagulation system closely linked with fibrotic events have been highlighted in the kidney. However, whether the coagulation system can affect the renal outcome of IgAN remains unclear. Herein, we investigated the association of coagulation parameters and pathological phenotype of IgAN and their combined effects on the deterioration of renal function.Methods. This retrospective study included N=291 patients with biopsy-proven IgAN from May 2009 to April 2013 in the Second Xiangya Hospital. Clinical data, pathological features were collected, and the associations of coagulation parameters at biopsy, T score, and renal outcome were evaluated. T score indicated the degree of tubular atrophy or interstitial fibrosis. The renal outcome was defined as an end-stage renal disease (ESRD) or an irreversible 50% estimated glomerular filtration rate (eGFR) reduction. Results. Shorter prothrombin time (PT) and the activated partial thromboplastin time (APTT) were significantly associated with T (both p<0.001). PT (<11.15s) or APTT (<29.65s) had worse cumulative survival rate (p=0.008, p=0.027 respectively) and were significantly but not independently associated with a higher risk of renal outcome (p=0.012, p=0.032 respectively). In the combined analyses of PT, APTT, and T lesions, the odd ratios for the outcome were significantly higher in the presence of T with PT (<11.15s) or APTT (<29.65s).Conclusion. Shorter PT and APTT are associated with an increased incidence of the T lesion and are additional factors that portend a poorer prognosis in IgAN. Monitoring coagulation function might be important when assessing the risk of progression. Additional studies exploring the molecular mechanism between coagulation and IgAN pathology are needed.

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“…(3) Moreover, extensive researches have found that coagulation is related to in ammatory response, and IgAN is also an in ammatory disease. IgAN patients commonly associated with alteration of various in ammatory cytokines [42], which may be related to the activation of procoagulant factors and renal brosis [43,44]. In addition, there are some limitations to our study.…”

Section: Discussionmentioning

confidence: 99%

Coagulation parameters are associated with the prognosis of immunoglobulin A nephropathy: a retrospective study

Xia

Liu

Peng

et al. 2020

Preprint

Self Cite

View full text Add to dashboard Cite

Background: Interstitial fibrosis/tubular atrophy (T) score is a known determinant of the progression of immunoglobulin A nephropathy (IgAN). Strong evidence indicates that the components of the coagulation system closely linked with fibrotic events and have been highlighted in the kidney. However, whether the coagulation system can affect the renal outcome of IgAN remains unclear. Herein, we investigated the association of coagulation parameters and pathological phenotype of IgAN and their combined effects on the deterioration of renal function.Methods: This retrospective study included patients with biopsy-proven IgAN from May 2009 to April 2013 in the Second Xiangya Hospital. Clinical data, pathological features were collected, and the associations of coagulation parameters at biopsy, T score, and renal outcome were evaluated. T score indicated the degree of tubular atrophy or interstitial fibrosis. The renal outcome was defined as an end-stage renal disease (ESRD) or an irreversible 50% estimated glomerular filtration rate (eGFR) reduction.Results: Shorter prothrombin time (PT) and the activated partial thromboplastin time (APTT) were significantly associated with T (both p<0.001). PT (<11.15s) or APTT (<29.65s) had worse cumulative survival rate (p=0.008, p=0.027 respectively) and were significantly but not independently associated with a higher risk of renal outcome (p=0.012, p=0.032 respectively). In the combined analyses of PT, APTT, and T lesions, the odd ratios for the outcome were significantly higher in the presence of T with PT (<11.15s) or APTT (<29.65s).Conclusion: Shorter PT and APTT are associated with an increased incidence of the T lesion and are additional factors that portend a poorer prognosis in IgAN. Monitoring coagulation function might be important when assessing the risk of progression. Additional studies exploring the molecular mechanism between coagulation and IgAN pathology are needed.

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Rapamycin Enhances Repressed Autophagy and Attenuates Aggressive Progression in a Rat Model of IgA Nephropathy

Cited by 27 publications

References 43 publications

Tripterygium glycoside protects against puromycin amino nucleoside‑induced podocyte injury by upregulating autophagy

Tripterygium glycoside protects against puromycin amino nucleoside‑induced podocyte injury by upregulating autophagy

Coagulation parameters are associated with the prognosis of immunoglobulin A nephropathy: a retrospective study

Coagulation parameters are associated with the prognosis of immunoglobulin A nephropathy: a retrospective study

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