scholarly journals TRPC6 channel activation promotes neonatal glomerular mesangial cell apoptosis via calcineurin/NFAT and FasL/Fas signaling pathways

2016 ◽  
Vol 6 (1) ◽  
Author(s):  
Hitesh Soni ◽  
Adebowale Adebiyi
Keyword(s):  
Signaling Pathways ◽  
Cell Apoptosis ◽  
Mesangial Cell ◽  
Glomerular Mesangial Cell ◽  
Channel Activation ◽  
Fas Signaling ◽  
Trpc6 Channel

scholarly journals Doxorubicin-Induced Fetal Mesangial Cell Death Occurs Independently of TRPC6 Channel Upregulation but Involves Mitochondrial Generation of Reactive Oxygen Species

2021 ◽  
Vol 22 (14) ◽  
pp. 7589
Author(s):  
Anberitha T. Matthews ◽  
Hitesh Soni ◽  
Katherine E. Robinson-Freeman ◽  
Theresa A. John ◽  
Randal K. Buddington ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Cell Death ◽  
Transient Receptor Potential ◽  
Mesangial Cell ◽  
Reactive Oxygen ◽  
Receptor Potential ◽  
Oxygen Species ◽  
Glomerular Mesangial Cell ◽  
Trpc6 Channel ◽  
Fetal Pig

Doxorubicin (DOX), a category D pregnancy drug, is a chemotherapeutic agent that has been shown in animal studies to induce fetal toxicity, including renal abnormalities. Upregulation of the transient receptor potential cation (TRPC) 6 channel is involved in DOX-induced podocyte apoptosis. We have previously reported that TRPC6-mediated Ca2+ signaling promotes neonatal glomerular mesangial cell (GMC) death. However, it is unknown whether DOX alters mesangial TRPC expression or viability in the fetus. In this study, cell growth was tracked in control and DOX-treated primary GMCs derived from fetal pigs. Live-cell imaging demonstrated that exposure to DOX inhibited the proliferation of fetal pig GMCs and induced cell death. DOX did not alter the TRPC3 expression levels. By contrast, TRPC6 protein expression in the cells was markedly reduced by DOX. DOX treatment also attenuated the TRPC6-mediated intracellular Ca2+ elevation. DOX stimulated mitochondrial reactive oxygen species (mtROS) generation and mitophagy by the GMCs. The DOX-induced mtROS generation and apoptosis were reversed by the mitochondria-targeted antioxidant mitoquinone. These data suggest that DOX-induced fetal pig GMC apoptosis is independent of TRPC6 channel upregulation but requires mtROS production. The mtROS-dependent GMC death may contribute to DOX-induced fetal nephrotoxicity when administered prenatally.

scholarly journals Sublytic C5b-9 Induces Glomerular Mesangial Cell Apoptosis through the Cascade Pathway of MEKK2–p38 MAPK–IRF-1–TRADD–Caspase 8 in Rat Thy-1 Nephritis

2016 ◽  
Vol 198 (3) ◽  
pp. 1104-1118 ◽  
Author(s):  
Ganqian Zhu ◽  
Wen Qiu ◽  
Yongting Li ◽  
Chenhui Zhao ◽  
Fengxia He ◽  
...  
Keyword(s):  
P38 Mapk ◽  
Cell Apoptosis ◽  
Mesangial Cell ◽  
Caspase 8 ◽  
Glomerular Mesangial Cell

scholarly journals Effect of recombinant Hepatitis B virus on human glomerular mesangial cell apoptosis

2014 ◽  
Vol 28 (4) ◽  
pp. 689-696 ◽  
Author(s):  
Yiguo Wang ◽  
Changhong Liu ◽  
Sen Hong ◽  
Pengju Zhang ◽  
Qian Liu
Keyword(s):  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Cell Apoptosis ◽  
Mesangial Cell ◽  
Recombinant Hepatitis ◽  
Glomerular Mesangial Cell ◽  
B Virus

Aldosterone-induced mesangial cell proliferation is mediated by EGF receptor transactivation

2009 ◽  
Vol 296 (6) ◽  
pp. F1323-F1333 ◽  
Author(s):  
Songming Huang ◽  
Aihua Zhang ◽  
Guixia Ding ◽  
Ronghua Chen
Keyword(s):  
Cell Proliferation ◽  
Signaling Pathways ◽  
Egf Receptor ◽  
Mesangial Cell ◽  
Oxidase Inhibitor ◽  
Akt Inhibitor ◽  
Glomerular Mesangial Cell ◽  
Egfr Transactivation ◽  
Cell Counts ◽  
Ribosomal S6 Kinase

Aldosterone (Aldo) stimulates glomerular mesangial cell (MC) proliferation, in part, through an ERK1/2-dependent pathway. In this study, we examined whether Aldo activation of ERK1/2 in MC is mediated through redox-dependent EGF receptor (EGFR) transactivation, as well as the involvement of other signaling mechanisms in Aldo-induced MC proliferation. Aldo increased human MC proliferation, as determined by [3H]thymidine incorporation and cell counts. This increase in proliferation was blocked by inhibition of the mineralocorticoid receptor (MR). Continuing our observations downstream in the signaling pathway, we examined the ability of Aldo to activate both the Ras/MAPK and the PI3K signaling pathways. Aldo increased Ki-RasA and Ki-RasA:GTP levels, and sequentially phosphorylated c-Raf, MAPK kinase (MEK1/2), and ERK1/2. Ki-RasA small interfering RNA (siRNA), the c-Raf inhibitor GW5074, and the MEK1/2 inhibitor PD98059 reduced Aldo-induced cell proliferation by ∼65%. Aldo also increased phosphorylation of PI3K, Akt, the mammalian target of rapamycin (mTOR), and the 70-kDa ribosomal S6 kinase (p70S6K1). Inhibition of the PI3K pathways by the selective PI3K inhibitor LY 294002, an Akt inhibitor, or the mTOR inhibitor rapamycin reduced cell proliferation by 51%. Combining LY 294002 and PD98059 completely blocked Aldo-induced MC proliferation. Next, we confirmed that Aldo exerts its effect on MAPK and PI3K activation, as well as on cell proliferation, by activating the EGFR. Pretreatment with the EGFR antagonist AG1478 inhibited MC proliferation, as well as the activation of Ras/MAPK and PI3K/Akt, suggesting that Ras/MAPK and PI3K/Akt activation occur downstream of EGFR activation. Finally, we examined the role of reactive oxygen species (ROS) in Aldo-induced transactivation of the EGFR. Aldo-induced ROS were predominantly generated by mitochondria. Pretreatment with the antioxidant N-acetyl-l-cysteine, catalase, SOD, mitochondrial respiratory chain complex I inhibitor rotenone (Rot), NADPH oxidase inhibitor apocynin, and DPI significantly inhibited Aldo-stimulated MC proliferation as well as EGFR transactivation. However, Rot reduced MC proliferation more potently than apocynin and DPI. In conclusion, Aldo stimulated cell proliferation through MR-mediated, redox-sensitive EGFR transactivation, which was dependent on the Ki-RasA/c-Raf/MEK/ERK and PI3K/Akt/mTOR/p70S6K1 signaling pathways in human MCs.

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