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STAT3 and ERK pathways are involved in cell growth stimulation of the ST2/IL1RL1 promoter.

ABSTRACT: The ST2 gene was originally identified as a primary responsive gene induced by stimulation with growth factors and by oncogenic stress. The ST2 gene harbors two distinct promoters - a distal promoter and a proximal promoter. In this study, we identified a novel type of serum-responsive element in the ST2 proximal promoter using reporter gene analysis; this element includes a possible responsive element for STAT family proteins. Indeed, enforced expression of constitutively active STAT3 activated this promoter element and induced the expression of ST2 gene products. Furthermore, an oncogenic Ras (G12V) mutant also caused the expression of ST2 gene products by utilizing the proximal promoter. We also clarified that activation of the ST2 promoter by either growth stimulation or oncogenic Ras was suppressed by the inhibitors for STAT3 and ERK pathways. Our observations strongly suggest the importance of STAT family and ERK pathways for the induction of ST2 gene products by cell growth stimulation.

SUBMITTER: Tago K

PROVIDER: S-EPMC5292660 | biostudies-literature | 2017 Feb

REPOSITORIES: biostudies-literature

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STAT3 and ERK pathways are involved in cell growth stimulation of the ST2/IL1RL1 promoter.

Tago Kenji K Ohta Satoshi S Funakoshi-Tago Megumi M Aoki-Ohmura Chihiro C Matsugi Jitsuhiro J Tominaga Shin-Ichi SI Yanagisawa Ken K

FEBS open bio 20170119 2

The ST2 gene was originally identified as a primary responsive gene induced by stimulation with growth factors and by oncogenic stress. The ST2 gene harbors two distinct promoters - a distal promoter and a proximal promoter. In this study, we identified a novel type of serum-responsive element in the ST2 proximal promoter using reporter gene analysis; this element includes a possible responsive element for STAT family proteins. Indeed, enforced expression of constitutively active STAT3 activated ...[more]

PMID: 28174694

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Project description:BackgroundMesangial proliferative glomerulonephritis (MsPGN) accounts for a main cause of chronic kidney disease (CKD), chronic renal failure and uremia. This paper aimed to examine the effect of Ntrk1 on MsPGN development, so as to identify a novel therapeutic target for MsPGN.MethodsThe MsPGN rat model was constructed by single injection of Thy1.1 monoclonal antibody via the tail vein. Additionally, the Ntrk1 knockdown rat model was established by injection of Ntrk1-RNAi lentivirus via the tail vein. Periodic acid-schiff staining and immunohistochemistry (IHC) were performed on kidney tissues. Moreover, the rat urinary protein was detected. Mesangial cells were transfected and treated with p38 inhibitor (SB202190) and ERK inhibitor (PD98059). Meanwhile, the viability and proliferation of mesangial cells were analyzed by cell counting kit-8 (CCK-8) and 5-Ethynyl-2'-deoxyuridine assays. Gene expression was detected by quantitative real-time polymerase chain reaction (qRT-PCR) and Western-blot (WB) assays.ResultsThe proliferation of mesangial cells was enhanced in glomerulus and Ki67 expression was up-regulated in renal tubule of MsPGN rats. The urine protein level increased in MsPGN rats. Pro-inflammatory factors and Ntrk1 expression were up-regulated in glomerulus of MsPGN rats. Ntrk1 up-regulation promoted the viability, proliferation, expression of pro-inflammatory factors and activation of the STAT3, p38 and ERK signaling pathways in mesangial cells. Ntrk1 knockdown reduced mesangial cell proliferation, urine protein, pro-inflammatory factors, activation of STAT3, p38 and ERK signaling pathways in glomerulus, and decreased Ki67 expression in renal tubule of MsPGN rats. Treatment with SB202190 and PD98059 reversed the effect of Ntrk1 on promoting the viability, proliferation and inflammatory response of mesangial cells.ConclusionNtrk1 promoted mesangial cell proliferation and inflammation in MsPGN rats by activating the STAT3 and p38/ERK MAPK signaling pathways.

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STAT3 and ERK pathways are involved in cell growth stimulation of the ST2/IL1RL1 promoter.

Publications

STAT3 and ERK pathways are involved in cell growth stimulation of the ST2/IL1RL1 promoter.

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