Zhen-wu-tang protects against podocyte injury in rats with IgA nephropathy via PPARγ/NF-κB pathway

Wang

et al. 2018

Front. Cell. Neurosci.

The blood-brain barrier (BBB) is a physical and biochemical barrier that maintains cerebral homeostasis. BBB dysfunction in an ischemic stroke, results in brain injury and subsequent neurological impairment. The aim of this study was to determine the possible protective effects of 1, 25-dihydroxyvitamin D3 [1, 25(OH)2D3, 1, 25-D3, vit D] on BBB dysfunction, at the early stages of an acute ischemic brain injury. We analyzed the effects of 1, 25-D3 on BBB integrity in terms of histopathological changes, the neurological deficit, infarct size and the expression of brain derived neurotrophic factor (BDNF), in a middle cerebral artery occlusion/reperfusion (MCAO/R) rat model. BBB permeability and the expression of permeability-related proteins in the brain were also evaluated by Evans blue (EB) staining and Western blotting respectively. To determine the possible mechanism underlying the role of 1, 25-D3 in BBB maintenance, after MCAO/R, the rats were treated with the specific peroxisome proliferator-activated receptor gamma (PPARγ) inhibitor GW9662. Supplementation with 1, 25-D3 markedly improved the neurological scores of the rats, decreased the infarct volume, prevented neuronal deformation and upregulated the expression of the tight junction (TJ) and BDNF proteins in their brains. Furthermore, it activated PPARγ but downregulated neuro-inflammatory cytokines such as nuclear factor kappa-B (NF-κB) and tumor necrosis factor-α (TNF-α), after MCAO/R. Taken together, 1, 25-D3 protects against cerebral ischemia by maintaining BBB permeability, upregulating the level of BDNF and inhibiting PPARγ-mediated neuro-inflammation.

Section: Introductionmentioning

confidence: 99%

RETRACTED: 1, 25-D3 Protects From Cerebral Ischemia by Maintaining BBB Permeability via PPAR-γ Activation

Wang

et al. 2018

Front. Cell. Neurosci.

“…The proteins of renal cortex tissue and HMCs were extracted and quantified as described previously (Liu et al, 2018). Proteins were loaded and separated in 10% SDS-PAGE, then transferred to polyvinylidene difluoride membranes (Millipore, MA, USA) using a Trans-Blot (Bio-rad, Berkeley, CA, USA).…”

Section: Methodsmentioning

confidence: 99%

Paeoniflorin Inhibits Mesangial Cell Proliferation and Inflammatory Response in Rats With Mesangial Proliferative Glomerulonephritis Through PI3K/AKT/GSK-3β Pathway

et al. 2019

Self Cite

Mesangial proliferative glomerulonephritis (MPGN) is the most common type of chronic kidney disease in China, characterized by mesangial cell proliferation and inflammatory response. Paeoniflorin, an effective composition extracted from Radix Paeoniae Alba, has been used for various kinds of kidney diseases. However, there are no studies reporting the effects of paeoniflorin on MPGN. The present study aims to investigate whether paeoniflorin plays a role in MPGN and confirm the underlying molecular mechanisms. Our results manifested that paeoniflorin strongly restrained 24 h urinary protein and promoted renal function and dyslipidemia in a MPGN rat model. Moreover, paeoniflorin attenuated mesangial cell proliferation and inflammation both in MPGN rats and human mesangial cells (HMCs) treated with lipopolysaccharide (LPS). In detail, paeoniflorin decreased the number of mesangial cells and expressions of proliferation marker Ki67 in MPGN rats. Paeoniflorin also inhibited HMC proliferation and blocked cell cycle progression. In addition, the contents of inflammatory factors and the expressions of macrophage marker iNOS were decreased after paeoniflorin treatment. Furthermore, we found that the protective effect of paeoniflorin was accompanied by a strong inhibition of the phosphatidylinositol 3-kinase (PI3K)/AKT/glycogen synthase kinase (GSK)-3β pathway. Paeoniflorin enhanced the inhibitory effect of PI3K inhibitor LY294002 and suppressed the activated effect of PI3K agonist insulin-like growth factor 1 (IGF-1) on PI3K/AKT/GSK-3β pathway. In conclusion, these results demonstrated that paeoniflorin ameliorates MPGN by inhibiting mesangial cell proliferation and inflammatory response through the PI3K/AKT/GSK-3β pathway.

“…ZWT is a traditional Chinese herbal prescription that has been widely applied to remedy many kidney diseases for years in China. In the previous study, we have proved that ZWT showed a good improvement effect on IgAN (Liu et al, 2018). However, the accurate pathogenetic mechanisms have not been fully acknowledged.…”

Section: Discussionmentioning

confidence: 93%

“…ZWT-containing serum (ZWTS) was manufactured as previously suggested (Liu et al, 2018). Concisely, fifty SD rats were randomly divided into two groups that one was treated with ZWT (16.8 g/kg), the other was treated with normal saline (10 ml/kg) to collect ZWTS and control serum (CS), respectively.…”

Section: Preparation Of Zwt-containing Serummentioning

confidence: 99%

“…ZWT could protect different kidney diseases by possessing properties of anti-inflammation ( Liu et al., 2016 ), antiapoptotic, ( Liu et al., 2017 ), anti-oxidant ( Li et al., 2018 ) and so on. Our previous study found that ZWT mitigated membranous nephropathy through depressing NF-κB pathway and NLRP3 inflammasome ( Liu et al., 2019 ).In addition, ZWT decreased proteinuria, alleviated kidney pathology and podocyte damage via blocking NF-κB pathway in IgAN rats model ( Liu et al., 2018 ). However, it is largely unclarified if ZWT protects against IgAN via regulating exosomes.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Zhen-Wu-Tang Protects IgA Nephropathy in Rats by Regulating Exosomes to Inhibit NF-κB/NLRP3 Pathway

et al. 2020

Front. Pharmacol.

Self Cite

Immunoglobulin A nephropathy (IgAN) is one of the most frequent kinds of primary glomerulonephritis characterized by IgA immune complexes deposition and glomerular proliferation. Zhen-wu-tang (ZWT), a well-known traditional Chinese formula has been reported to ameliorate various kidney diseases. However, its pharmacological mechanism remains unclear. Exosomes have been described in diverse renal diseases by mediating cellular communication but rarely in the IgAN. The purpose of the present study is to explore whether the underlying mechanisms of the effect of ZWT on IgAN is correlated to exosomes. Our results demonstrated that in human renal tubular epithelial cells (HK-2) stimulated by lipopolysaccharide, exosomes are obviously released after ZWT-containing serum treatment especially with 10% ZWT. In addition, once released, HK-2-derived exosomes were uptaked by human mesangial cells (HMC), which impeded the activation of NF-kB/NLRP3 signaling pathway to exert anti-inflammatory effects in a lipopolysaccharide induced proliferation model. Moreover, IgAN rat model was established by bovine serum albumin, CCL 4 mixed solution and LPS. We found that 10% ZWT could significantly promote the release of exosomes from HK-2 and inhibit HMC proliferation to improve inflammation. Thus HK-2-derived exosomes treated with 10% ZWT (ZWT-EXO) were administered to the rats by tail vein injection. Our results showed that ZWT-EXO decreased the levels of 24 h proteinuria, urinary erythrocyte, IgA deposition in glomerulus and renal pathological injury which ameliorated the kidney damage. In addition, ZWT was able to dramatically promote secretion of exosomes in renal tissues while blocked NF-kB nuclear translocation as well as activation of NLRP3 inflammasome, leading to the inhibition of IL-1b and caspase-1. In conclusion, our study reveal that ZWT has protective effects on IgAN by regulating exosomes secretion to inhibit the activation of NF-kB/NLRP3 pathway, thereby attenuating the renal dysfunction. These findings may provide a new therapeutic target for the treatment of IgAN.