Feedback Regulation of PRL Secretion Is Mediated by the Transcription Factor, Signal Transducer, and Activator of Transcription 5b

Abstract GH plays a central role in controlling somatic growth, tissue regeneration, and intermediary metabolism in most vertebrate species through mechanisms dependent on the regulation of gene expression. Recent studies using transcript profiling have identified large cohorts of genes whose expression is induced by GH. Other results have demonstrated that signal transducer and activator of transcription (Stat) 5b, a latent transcription factor activated by the GH receptor-associated protein kinase, Jak2, is a key agent in the GH-stimulated gene activation that leads to somatic growth. By contrast, little is known about the steps through which GH-initiated signaling pathways reduce gene expression. Here we show that Stat5b plays a critical role in the GH-regulated inhibition of IGF binding protein-1 gene transcription by impairing the actions of the FoxO1 transcription factor on the IGF binding protein-1 promoter. Additional observations using transcript profiling in the liver indicate that Stat5b may be a general mediator of GH-initiated gene repression. Our results provide a model for understanding how GH may simultaneously stimulate and inhibit the expression of different cohorts of genes via the same transcription factor, potentially explaining how GH action leads to integrated biological responses in the whole organism.

Download Full-text

Arabidopsis Transcription Factor ELONGATED HYPOCOTYL5 Plays a Role in the Feedback Regulation of Phytochrome A Signaling

The Plant Cell ◽

10.1105/tpc.110.075788 ◽

2010 ◽

Vol 22 (11) ◽

pp. 3634-3649 ◽

Cited By ~ 73

Author(s):

Jigang Li ◽

Gang Li ◽

Shumin Gao ◽

Cristina Martinez ◽

Guangming He ◽

...

Keyword(s):

Transcription Factor ◽

Feedback Regulation ◽

Phytochrome A

Download Full-text

The prenylflavonoid Icaritin enhances osteoblast proliferation and function by signal transducer and activator of transcription factor 3 (STAT-3) regulation of C-X-C chemokine receptor type 4 (CXCR4) expression

Bone ◽

10.1016/j.bone.2017.08.028 ◽

2017 ◽

Vol 105 ◽

pp. 122-133 ◽

Cited By ~ 5

Author(s):

RZL Lim ◽

L. Li ◽

N. Chew ◽

E.L. Yong

Keyword(s):

Transcription Factor ◽

Chemokine Receptor ◽

Cxcr4 Expression ◽

Receptor Type ◽

Signal Transducer ◽

Osteoblast Proliferation ◽

And Function ◽

Transcription Factor 3

Download Full-text

Apatinib Inhibits Angiogenesis in Intrahepatic Cholangiocarcinoma by Regulating the Vascular Endothelial Growth Factor Receptor-2/Signal Transducer and Activator of Transcription Factor 3/Hypoxia Inducible Factor 1 Subunit Alpha Signaling Axis

Pharmacology ◽

10.1159/000514410 ◽

2021 ◽

pp. 1-11

Author(s):

Man-Ping Huang ◽

Shan-Zhi Gu ◽

Bin Huang ◽

Guo-Wen Li ◽

Zheng-Ping Xiong ◽

...

Keyword(s):

Vascular Endothelial Growth Factor ◽

Transcription Factor ◽

Growth Factor ◽

Intrahepatic Cholangiocarcinoma ◽

Hypoxia Inducible Factor ◽

Growth Factor Receptor ◽

Vascular Endothelial ◽

Signal Transducer ◽

Hypoxia Inducible Factor 1 ◽

Endothelial Growth Factor

Introduction: Intrahepatic cholangiocarcinoma (ICC), which is difficult to diagnose and is usually fatal due to its late clinical presentation and a lack of eﬀective treatment, has risen over the past decades but without much improvement in prognosis. Objective: The study aimed to investigate the role of apatinib that targets vascular endothelial growth factor receptor-2 (VEGFR2) in ICC. Methods: MTT assays, cell scratch assays, and tube formation assays were used to assess the effect of apatinib on human ICC cell line (HuCCT-1) and RBE cells proliferation, migration, and angiogenic capacity, respectively. Expression of vascular endothelial growth factor (VEGF), VEGFR2, signal transducer and activator of transcription factor 3 (STAT3), pSTAT3, and hypoxia inducible factor 1 subunit alpha (HIF-1α) pathway proteins was assessed using Western blotting and mRNA expression analysis in HuCCT-1 was performed using RT-qPCR assays. The pcDNA 3.1(-)-VEGFR2 and pcDNA 3.1(-)-HIF-1α were transfected into HuCCT-1 and RBE cells using Lipofectamine 2,000 to obtain overexpressed HuCCT-1 and RBE cells. Results: We found that apatinib-inhibited proliferation, migration, and angiogenesis of HuCCT-1 and RBE cells in vitro in a dose-dependent manner. We also proved that apatinib effectively inhibits angiogenesis in tumor cells by blocking the expression of VEGF and VEGFR2 in these cells. In addition, we demonstrated that apatinib regulates the expression of STAT3 phosphorylation by inhibiting VEGFR2. Finally, we showed that apatinib regulates ICC angiogenesis and HIF-1α/VEGF expression via STAT3. Conclusions: Based on the above findings, we conclude that apatinib inhibits HuCCT-1 and RBE cell proliferation, migration, and tumor angiogenesis by inhibiting the VEGFR2/STAT3/HIF-1α axis signaling pathway. Apatinib can be a promising drug for ICC-targeted molecular therapy.

Download Full-text