Lysophosphatidic acid increases mesangial cell proliferation in models of diabetic nephropathy via Rac1/MAPK/KLF5 signaling

Abnormal and excessive growth of mesangial cells is important in the pathophysiologic processes of diabetes-associated interstitial fibrosis and glomerulosclerosis, leading to diabetic nephropathy, which eventually turns into end-stage renal disease. Sauchinone, a biologically-active lignan isolated from aerial parts of Saururus chinensis, has anti-inflammatory and anti-viral activities effects on various cell types. However, there are no studies reporting the effects of sauchinone on diabetic nephropathy. The present study aims to investigate the role of sauchinone in mesangial cell proliferation and fibrosis induced by angiotensin II, as well as the underlying mechanisms of these processes. Human renal mesangial cells were induced by angiotensin II (AngII, 10 μM) in the presence or absence of sauchinone (0.1–1 μM) and incubated for 48 h. In this study, we found that AngII induced mesangial cell proliferation, while treatment with sauchinone inhibited the cell proliferation in a dose-dependent manner. Pre-treatment with sauchinone induced down-regulation of cyclins/CDKs and up-regulation of CDK inhibitor, p21, and p27kip1 expression. In addition, AngII-enhanced expression of fibrosis biomarkers such as fibronectin, collagen IV, and connective tissue growth factor (CTGF), which was markedly attenuated by sauchinone. Sauchinone also decreased AngII-induced TGF-β1 and Smad-2, Smad-3, and Smad-4 expression. This study further revealed that sauchinone ameliorated AngII-induced mesangial inflammation through disturbing activation of inflammatory factors, and NLRP3 inflammasome, which is composed of the NLRP3 protein, procaspase-1, and apoptosis-associated speck-like protein containing a CARD (ASC). Moreover, pretreatment of sauchinone inhibited NF-κB translocation and ROS production in AngII-exposed mesangial cells. These data suggest that sauchinone has a protective effect on renal proliferation, fibrosis and inflammation. Therefore, sauchinone might be a potential pharmacological agent in prevention of AngII-induced renal damage leading to diabetic nephropathy.

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Triptolide Suppresses Glomerular Mesangial Cell Proliferation in Diabetic Nephropathy Is Associated with Inhibition of PDK1/Akt/mTOR Pathway

International Journal of Biological Sciences ◽

10.7150/ijbs.20485 ◽

2017 ◽

Vol 13 (10) ◽

pp. 1266-1275 ◽

Cited By ~ 19

Author(s):

Fei Han ◽

Mei Xue ◽

Yunpeng Chang ◽

Xiaoyu Li ◽

Yang Yang ◽

...

Keyword(s):

Cell Proliferation ◽

Diabetic Nephropathy ◽

Mesangial Cell ◽

Mtor Pathway ◽

Glomerular Mesangial Cell ◽

Mesangial Cell Proliferation

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Effect of Sphingosine-1-phosphate and Analogues of Lysophosphatidic Acid on Mesangial Cell Proliferation

Annals of the New York Academy of Sciences ◽

10.1111/j.1749-6632.2000.tb06574.x ◽

2006 ◽

Vol 905 (1) ◽

pp. 340-343 ◽

Cited By ~ 6

Author(s):

ISABELLE GENNERO ◽

MARIE FRANÇOISE SIMON ◽

FRÉDÉRIQUE GAITS ◽

CLOTILDE CARIVEN ◽

PIERRE ROGALLE ◽

...

Keyword(s):

Cell Proliferation ◽

Lysophosphatidic Acid ◽

Mesangial Cell ◽

Mesangial Cell Proliferation ◽

Sphingosine 1 Phosphate

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Knock-Down of Long Non-Coding RNA ANRIL Suppresses Mouse Mesangial Cell Proliferation, Fibrosis, Inflammation via Regulating Wnt/β-Catenin and MEK/ERK Pathways in Diabetic Nephropathy

Experimental and Clinical Endocrinology & Diabetes ◽

10.1055/a-1185-9283 ◽

2020 ◽

Author(s):

Xun Fang ◽

Jun Hu ◽

Hongyan Zhou

Keyword(s):

Cell Proliferation ◽

Diabetic Nephropathy ◽

Mesangial Cell ◽

Mesangial Cells ◽

Necrosis Factor Alpha ◽

Monocyte Chemoattractant Protein 1 ◽

Knock Down ◽

Non Coding Rna ◽

Mesangial Cell Proliferation ◽

Long Non Coding Rna

Abstract Aims Our study aimed to investigate the role of long non-coding RNA ANRIL (lnc-ANRIL) knock-down in regulating cell activities, inflammation and downstream signaling pathways in mouse mesangial cellular diabetic nephropathy (DN) model. Methods The mouse mesangial cells (SV40-MES13 cells) were treated with high-glucose (HG) to construct cellular DN model. Lnc-ANRIL knock-down plasmid and control knock-down plasmid were transfected into HG-treated SV40-MES13 cells as Sh-ANRIL group and Sh-NC group respectively. Results Lnc-ANRIL expression was significantly higher in HG-treated SV40-MES13 cells compared with normal glucose-treated SV40-MES13 cells and osmotic control-treated SV40-MES13 cells. Lnc-ANRIL knock-down suppressed cell proliferation and promoted cell apoptosis in HG-treated SV40-MES13 cells. As for fibrosis, lnc-ANRIL knock-down reduced fibronectin and collagen I expressions in HG-treated SV40-MES13 cells. Besides, the expressions of supernatant tumor necrosis factor-alpha (TNF-α), monocyte chemoattractant protein-1 (MCP-1), interleukin (IL)-1β, IL-6, IL-8 and IL-18 were reduced in Sh-ANRIL group compared with Sh-NC group. Furthermore, Wnt3, β-catenin, p-MEK1 and p-ERK1 expressions were suppressed in Sh-ANRIL group compared with Sh-NC group, which suggested that lnc-ANRIL knock-down inhibited Wnt/β-catenin and MEK/ERK pathways in HG-treated SV40-MES13 cells. Conclusions Lnc-ANRIL knock-down suppresses mouse mesangial cell proliferation, fibrosis, inflammation, Wnt/β-catenin and MEK/ERK pathways in DN.

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Bimodal effects of platelet-derived growth factor on rat mesangial cell proliferation and death, and the role of lysophosphatidic acid in cell survival

Clinical Science ◽

10.1042/cs1010011 ◽

2001 ◽

Vol 101 (1) ◽

pp. 11-19 ◽

Cited By ~ 9

Author(s):

Chiyoko N. INOUE ◽

Isao NAGANO ◽

Ryo ICHINOHASAMA ◽

Natsumi ASATO ◽

Yoshiaki KONDO ◽

...

Keyword(s):

Cell Proliferation ◽

Cell Death ◽

Growth Factor ◽

Lysophosphatidic Acid ◽

Culture Medium ◽

Mesangial Cell ◽

Mesangial Cells ◽

Platelet Derived Growth Factor ◽

P53 Expression ◽

Mesangial Cell Proliferation

Although mesangial cell death has been shown to be correlated with mesangial cell mitosis in vivo, little is known about how these two apparently opposite events are regulated. We show that the addition of platelet-derived growth factor (PDGF; 10–50 ng/ml) to primary cultured rat mesangial cells for 24 h caused continuous proliferation along with simultaneous cell death. This process was accompanied by the fragmentation of DNA into nucleosomal oligomers, the development of apoptotic morphological changes in the nucleus, and increased expression of p53. Accumulation of lactate dehydrogenase (LDH) was also observed in the culture medium, suggesting that both apoptosis and necrosis are involved in the cell death mechanisms observed. We also observed that addition of 30 µM lysophosphatidic acid (LPA) to the culture medium greatly suppressed PDGF-induced cell death, leading to synergistically enhanced mesangial cell proliferation. DNA fragmentation, p53 expression and LDH release were all suppressed by LPA. We suggest that PDGF is a bifunctional molecule in mesangial cells that evokes both cell proliferation and cell death simultaneously, whereas LPA is a survival factor. We speculate that PDGF and LPA may play important roles in the progression or exacerbation of proliferative glomerulonephritis.

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