Serum secretory phospholipase A2 group IB correlates with the severity of membranous nephropathy

Li, Weihao; Zhang, Mingming; Yaping, Guo; Liu, Xiaomei; X, Ji; Su, Junhua; Zhang, Zhiping; Zhang, Feifei

doi:10.1016/j.cca.2018.04.009

Cited by 9 publications

(11 citation statements)

References 27 publications

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“…This study found that serum levels of sPLA2-IB were significantly higher in the high proteinuria group than in the low proteinuria group and positively correlated with proteinuria, consistent with Li, W. studies, 5 indicating that sPLA2-IB as a molecular indicator of proteinuria in IMN patients. In addition, serum levels of sPLA2-IB were confirmed to increase with the pathological stage of IMN, displaying that sPLA2-IB reflects the severity of pathological changes, and in vitro studies have shown that sPLA2-IB-induced podocyte apoptosis via PLA2R, 6 suggesting that sPLA2-IB might participate in the pathogenesis of IMN by inducing podocyte injury.…”

Section: Discussionsupporting

confidence: 88%

“…The serum sPLA2-IB levels were measured by enzyme-linked immunosorbent assay (ELISA) reagent (Elabscience, China). 5 A plate reader (SpectraMax i3x, USA) was used to read the absorbance at 450 nm.…”

Section: Measurement Of Serum Spla2-ibmentioning

confidence: 99%

“…Recently, secretory phospholipase A2 group IB (sP-LA2-IB), as a ligand of PLA2R, has raised concern, and the serum sPLA2-IB level in IMN has been known to be closely associated with proteinuria and remission. 5,6 Moreover, PLA2R has been verified to be an important receptor involved in physiological and pathological processes by binding sPLA2-IB. 6,7 In our previous study, we also confirmed that sPLA2-IB-induced podocyte apoptosis via PLA2R.…”

Section: Introductionmentioning

confidence: 99%

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sPLA2‐IB and PLA2R mediate insufficient autophagy and contribute to podocyte injury in idiopathic membranous nephropathy by activation of the p38MAPK/mTOR/ULK1 ^ser757 signaling pathway

Yang

Lin

et al. 2020

FASEB j.

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Secretory phospholipase A2 group IB (sPLA2-IB) and M-type phospholipase A2 receptor (PLA2R) are closely associated with proteinuria in idiopathic membranous nephropathy (IMN). Podocytes constitute an important component of glomerular filtration, and high basal autophagy is indispensable for podocyte function. The current study aimed to analyze the relationship between sPLA2-IB and podocyte autophagy in IMN and determine whether sPLA2-IB mediates abnormal autophagy regulation in podocytes. The serum sPLA2-IB level and podocyte autophagy were detected, and clinical data were collected from IMN patients with different proteinuria levels. Then, the effects of sPLA2-IB on autophagy signaling pathways were evaluated in cultured human podocytes treated with sPLA2-IB, rapamycin, p38 inhibition, and PLA2R-siRNA in vitro. We found that IMN patients with nephrotic-range proteinuria have a significantly higher level of sPLA2-IB and fewer autophagosomes than those with non-nephrotic-range proteinuria. In vitro sPLA2-IB-induced insufficient autophagy in podocytes and promoted podocyte injury via activation of the mTOR/ULK1 ser757 signaling pathway. Moreover, inhibition of p38 MAPK evidently abrogated sPLA2-IB-induced autophagy and the activation of mTOR/ULK1 ser757 . Additionally, PLA2R silencing demonstrated that sPLA2-IB-induced abnormal autophagy was also PLA2R-dependent. In conclusion, the results revealed that sPLA2-IB downregulated autophagy and contributed to podocyte injury via PLA2R though activation of the p38MAPK/mTOR/ULK1 ser757 signaling pathway.

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Section: Discussionsupporting

confidence: 88%

Section: Measurement Of Serum Spla2-ibmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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sPLA2‐IB and PLA2R mediate insufficient autophagy and contribute to podocyte injury in idiopathic membranous nephropathy by activation of the p38MAPK/mTOR/ULK1 ^ser757 signaling pathway

Yang

Lin

et al. 2020

FASEB j.

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“…Circulating anti-PLA2R antibodies correlate with the degree of proteinuria [47,48], disappear before clinical remission of NS and reappear before clinical relapse (immunological remission occurs prior to clinical remission) [49], predict less response to immunosuppression [50,51] and indicate lower spontaneous remission rate [48,52,53]. A high level of antibodies predicts longer time to remission [48,54] and higher risk of the doubling of serum creatinine and poor kidney outcomes [48,55,56].…”

Section: Anti-phospholipase A2 Receptor and Anti-thrombospondin Domain 7a Antibodiesmentioning

confidence: 99%

Molecular classification of membranous nephropathy

Pozdzik

Touzani

Brochériou

et al. 2019

Current Opinion in Nephrology and Hypertension

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Purpose of review Continuous expansion of our knowledge in the pathogenesis of membranous nephropathy possible by the identification of antibodies recognized specific podocytes antigens results in unprecedent patient management strategy. Recent findingsCirculating anti-phospholipase A2 receptor (PLA2R) and anti-thrombospondin domain 7A (THSD7A) antibodies strongly relate with the modifications of podocytes biology leading to the new molecular diagnosis of membranous nephropathy. Immunization against THSD7A involves extra-renal mechanism. However, the pathway of anti-PLA2R immunization still remains unresolved. Experimental data highlight the crucial role of THSD7A in the attachment of podocytes to the glomerular basement membrane, rewarding the THSD7A pathogenicity, whereas the third of Koch's postulates is still not fulfilled for anti-PLA2R antibodies. The anti-PLA2R antibodies epitope spreading will possibly be even more specific marker improving the molecular classification of membranous nephropathy. Two immune epitopes have been identified in the N-terminal tail of THSD7A but without evidence of epitope spreading as for anti-PLA2R.

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“…Outcome of disease is variable, ranging from spontaneous remission to progressive renal failure reaching end stage renal disease [1][2][3][4]. Undoubtedly, after the discovery of innovative pathogenic antibodies, the M-type phospholipase A2 receptor (PLA2R), we are on the way to changing our aspect on the disease, in terms of research and clinical management [5][6][7]. However, critical questions regarding diagnostic approach and follow up, assessment of renal biopsy findings, and most importantly, selecting and applying the best therapeutic regime for each patient still remain.…”

Section: Introductionmentioning

confidence: 99%

Immunosuppressive regimens based on Cyclophospamide or Calcineurin inhibitors: Comparison of their effect in the long term outcome of Primary Membranous Nephropathy

Stangou

Marinaki

Papachristou

et al. 2019

Preprint

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Management of the Primary Membranous Nephropathy (PMN) usually involves administration of immunosuppressives. Cyclophosphamide (Cyclo) and Calcineurin Inhibitors (CNIs) are both widely used but only limited data exist to compare their efficacy in long term follow-up.Aim of the present study was to estimate and compare long term effects of Cyclo and CNIs in patients with PMN.Patients-Methods. Clinical data, histologic findings and long term outcome were retrospectively studied. The response to treatment and rate of relapse was compared between patients treated with CNIs or Cyclo based immunosuppressive regimens.Results. Twenty three centers participated in the study, with 752 PMN patients (Mean age 53.4(14-87)yrs, M/F 467/285), followed for 10.1±5.7 years. All patients were initially treated with Renin Angiotensin Aldosterone System inhibitors (RAASi) for at least 6 months. Based on their response and tolerance to initial treatment, patients were divided into 3 groups, group I with spontaneous remission, who had no further treatment, group II, continued on RAASi only, and group III on RAASi+immunosuppression. Immunosuppressive regimes were mainly based on CNIs or Cyclo. Frequent relapses and failure to treatment were more common between patients who had started on CNIs (n=381) compared to those initially treated with Cyclo (n=110), relapse rate: 25.2% vs. 6.4%, p<0.0001, and no response rate: 22.5% vs. 13.6%, p=0.04, respectively. Conclusions.Long term follow up showed that administration of Cyclo in PMN is followed by better preservation of renal function, increased response rate and less frequent relapses, compared to CNIs.

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Serum secretory phospholipase A2 group IB correlates with the severity of membranous nephropathy

Cited by 9 publications

References 27 publications

sPLA2‐IB and PLA2R mediate insufficient autophagy and contribute to podocyte injury in idiopathic membranous nephropathy by activation of the p38MAPK/mTOR/ULK1 ^ser757 signaling pathway

sPLA2‐IB and PLA2R mediate insufficient autophagy and contribute to podocyte injury in idiopathic membranous nephropathy by activation of the p38MAPK/mTOR/ULK1 ^ser757 signaling pathway

Molecular classification of membranous nephropathy

Immunosuppressive regimens based on Cyclophospamide or Calcineurin inhibitors: Comparison of their effect in the long term outcome of Primary Membranous Nephropathy

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Serum secretory phospholipase A2 group IB correlates with the severity of membranous nephropathy

Cited by 9 publications

References 27 publications

sPLA2‐IB and PLA2R mediate insufficient autophagy and contribute to podocyte injury in idiopathic membranous nephropathy by activation of the p38MAPK/mTOR/ULK1 ser757 signaling pathway

sPLA2‐IB and PLA2R mediate insufficient autophagy and contribute to podocyte injury in idiopathic membranous nephropathy by activation of the p38MAPK/mTOR/ULK1 ser757 signaling pathway

Molecular classification of membranous nephropathy

Immunosuppressive regimens based on Cyclophospamide or Calcineurin inhibitors: Comparison of their effect in the long term outcome of Primary Membranous Nephropathy

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sPLA2‐IB and PLA2R mediate insufficient autophagy and contribute to podocyte injury in idiopathic membranous nephropathy by activation of the p38MAPK/mTOR/ULK1 ^ser757 signaling pathway

sPLA2‐IB and PLA2R mediate insufficient autophagy and contribute to podocyte injury in idiopathic membranous nephropathy by activation of the p38MAPK/mTOR/ULK1 ^ser757 signaling pathway