PLA2G12B mediates arachidonic acid metabolism through activation of the NF-κB pathway to promote membrane nephropathy.INTRODUCTION
 Phospholipases A2, Group XII B (PLA2G12B) was reported involved in the regulation of MN by interfering with arachidonic acid (AA) metabolism, but there is a lack of sufficient evidence.  In this study, we investigated the role and molecular mechanism of PLA2G12B in MN.


 C57BL/6 mice were used to established MN model to extract primary podocytes, then divided into control, model, si- Phospholipases A2 receptor (PLA2R), PLA2G12B, PLA2G12B+ si-PLA2R, PLA2G12B+nuclear factor kappa-B (NF-κB) inhibitor, PLA2G12B+ NF-κB inhibitor+si-PLA2R groups.  The results revealed that AA metabolites were activated in the MN model mice and the expression of PLA2G12B and NF-κB pathway levels were elevated.  Besides, cellular experiments demonstrated that prostaglandin I2 (PGI2), thromboxane A2 (TXA2) and leukotriene B4 (LTB4) and NF-κB pathway were significantly increased in the PLA2G12B group.  Also, PLA2G12B promotes apoptosis and suppresses cell activity in podocytes, and these effects could be antagonized by NF-κB inhibitors.  Promotional effects of PLA2G12B in primary MN are associated with the regulation of AA metabolism and NF-κB pathway.
PLA2G12B
PLA2G12B mediates arachidonic acid metabolism through activation of the NF-κB pathway to promote membrane nephropathy.INTRODUCTION
 C57BL/6 mice were used to established MN model to extract primary podocytes, then divided into control, model, si- Phospholipases A2 receptor (PLA2R), PLA2G12B, PLA2G12B+ si-PLA2R, PLA2G12B+nuclear factor kappa-B (NF-κB) inhibitor, PLA2G12B+ NF-κB inhibitor+si-PLA2R groups.  The results revealed that AA metabolites were activated in the MN model mice and the expression of PLA2G12B and NF-κB pathway levels were elevated.  Besides, cellular experiments demonstrated that prostaglandin I2 (PGI2), thromboxane A2 (TXA2) and leukotriene B4 (LTB4) and NF-κB pathway were significantly increased in the PLA2G12B group.  Also, PLA2G12B promotes apoptosis and suppresses cell activity in podocytes, and these effects could be antagonized by NF-κB inhibitors.  Furthermore, with the inference of si-PLA2R, the NF-κB inhibitors' effects were reversed.


 Promotional effects of PLA2G12B in primary MN are associated with the regulation of AA metabolism and NF-κB pathway.
NF-κB
Genes and proteins associated with metabolism and inflammatory factors were detected by qRT-PCR, and western blot.



qRT-PCR
Genes and proteins associated with metabolism and inflammatory factors were detected by qRT-PCR, and western blot.



western blot
Hematoxylin-Eosin (HE) staining and immunofluorescence were used to detect kidneys histological arrangement, serum levels of cholesterol related indices and AA. 
immunofluorescence