Chemical Inhibition of JAK2 Mimics Genetic Ablation of Uterine Function of Leukemia Inhibitory Factor

Chemical Inhibition of JAK2 Mimics Genetic Ablation of Uterine Function of Leukemia Inhibitory Factor

Jrgang Cheng

Contact

Colin L. Stewart

Contact

National Cancer Institute

Chemical Inhibition of JAK2 Mimics Genetic Ablation of Uterine Function of Leukemia Inhibitory Factor

Article Fingerprint

ReserarchID

24ZA7

Chemical Inhibition of JAK2 Mimics Genetic Ablation of Uterine Function of Leukemia Inhibitory Factor Banner

AI TAKEAWAY

Connecting with the Eternal Ground

Abstract

Uterine receptivity needs to be synchronized with embryonic development, so the blastocyst stage of the embryo can implant. Leukemia Inhibitory Factor (LIF) is an essential factor for implantation, which is involved in the initiation of the window of implantation. However, the process by which the LIF signal pathway is transduced in the uterine luminal epithelium (LE) that leads to uterine receptivity is not completely elucidated. We tested the ability of cellular signaling inhibitors to disrupt uterine support of the embryo. Only Tyrphostin-AG490, an inhibitor of Jak2, can interfere with LIF signaling. Not only can AG490 reduce phosphorylated STAT3 levels in isolated LE, but it also ablated implantation when injected into uterine lumen. Furthermore, AG490 treatment in wild-type animals mimics the consequences of genetic ablation of LIF that results in free floating hatched embryos, which are unable to implant. Our results support the notion that Jak2 is the sole Janus kinase to mediate LIF activation in LE, and the signaling pathways of cytokines can serve as contraception targets.

References

14 Cites in Article

Reference Format

B Paria,H Song,S Dey (2001). Implantation: molecular basis of embryo-uterine dialogue.
C Finn,L Martin (1974). THE CONTROL OF IMPLANTATION.
J Mccormack,G Greenwald (1974). Progesterone and oestradiol-17beta concentrations in the peripheral plasma during pregnancy in the mouse.
J Mccormack,G Greenwald (1974). Evidence for a preimplantation rise in oestradiol-17beta levels on day 4 of pregnancy in the mouse.
J Chen,J Cheng,T Shatzer,L Sewell,L Hernandez,C Stewart (2000). Leukemia inhibitory factor can substitute for nidatory estrogen and is essential to inducing a receptive uterus for implantation but is not essential for subsequent embryogenesis.
Colin Stewart,Petr Kaspar,Lisa Brunet,Harshida Bhatt,Inder Gadi,Frank Köntgen,Susan Abbondanzo (1992). Blastocyst implantation depends on maternal expression of leukaemia inhibitory factor.
S Kimber (2005). Leukaemia inhibitory factor in implantation and uterine biology.
J Cheng,J Chen,L Hernandez,W Alvord,C Stewart (2001). Dual control of LIF expression and LIF receptor function regulate Stat3 activation at the onset of uterine receptivity and embryo implantation.
J Cheng,C Rodriguez,C Stewart (2002). Control of uterine receptivity and embryo implantation by steroid hormone regulation of LIF production and LIF receptor activity: towards a molecular understanding of "the window of implantation.
M Ernst,A Oates,A Dunn (1996). Gp130-mediated signal transduction in embryonic stem cells involves activation of Jak and Ras/mitogen-activated protein kinase pathways.
C Auernhammer,S Melmed (2000). Leukemiainhibitory factor-neuroimmune modulator of endocrine function.
R Bigsby,P Cooke,G Cunha (1986). A simple efficient method for separating murine uterine epithelial and mesenchymal cells.
T Boulton,Z Zhong,Z Wen,J Darnell,N Stahl,G Yancopoulos (1995). STAT3 activation by cytokines utilizing gp130 and related transducers involves a secondary modification requiring an H7sensitive kinase.
M Narazaki,B Witthuhn,K Yoshida,O Silvennoinen,K Yasukawa,J Ihle,T Kishimoto,T Taga (1994). Activation of JAK2 kinase mediated by the V. Acknowledgments.

Download References

Funding

No external funding was declared for this work.

Conflict of Interest

The authors declare no conflict of interest.

Ethical Approval

No ethics committee approval was required for this article type.

Data Availability

Not applicable for this article.

How to Cite This Article

Jrgang Cheng. 2016. \u201cChemical Inhibition of JAK2 Mimics Genetic Ablation of Uterine Function of Leukemia Inhibitory Factor\u201d. Global Journal of Medical Research - K: Interdisciplinary GJMR-K Volume 16 (GJMR Volume 16 Issue K2).

More Citation Formats

Select Citation Style:

Download Citation

GJMR Volume 16 Issue K2

Explore Journals Explore Volume Read This Issue

Journal Specifications

Crossref Journal DOI 10.17406/gjmra

Print ISSN 0975-5888

e-ISSN 2249-4618

Keywords

Not Found

Classification

GJMR-K Classification NLMC Code: WP 440

Submission ReceivedDecember 10, 2015
Peer Review Double Blind
Handling Editor
Accepted December 31, 2015
Published January 15, 2016

Version of record

v1.2

Issue date

May 12, 2016

Language

Experiance in AR

Explore published articles in an immersive Augmented Reality environment. Our platform converts research papers into interactive 3D books, allowing readers to view and interact with content using AR and VR compatible devices.

View in VR

Read in 3D

Your published article is automatically converted into a realistic 3D book. Flip through pages and read research papers in a more engaging and interactive format.

View in 3D

Article Matrices

Total Score: 132

Country: United States

Subject: Global Journal of Medical Research - K: Interdisciplinary

Authors: Jrgang Cheng, Colin L. Stewart (PhD/Dr. count: 0)

View Count (all-time): 174

Total Views (Real + Logic): 3929

Total Downloads (simulated): 2022

Publish Date: 2016 05, Thu

Monthly Totals (Real + Logic):

Month 1: 50 views
Month 2: 61 views
Month 3: 55 views
Month 4: 36 views
Month 5: 34 views
Month 6: 18 views
Month 7: 50 views
Month 8: 27 views
Month 9: 40 views
Month 10: 30 views
Month 11: 27 views
Month 12: 23 views
Month 13: 35 views
Month 14: 28 views
Month 15: 36 views
Month 16: 22 views
Month 17: 23 views
Month 18: 33 views
Month 19: 25 views
Month 20: 23 views
Month 21: 42 views
Month 22: 29 views
Month 23: 29 views
Month 24: 29 views
Month 25: 33 views
Month 26: 31 views
Month 27: 37 views
Month 28: 21 views
Month 29: 22 views
Month 30: 43 views
Month 31: 30 views
Month 32: 27 views
Month 33: 40 views
Month 34: 24 views
Month 35: 29 views
Month 36: 12 views
Month 37: 32 views
Month 38: 29 views
Month 39: 14 views
Month 40: 47 views
Month 41: 23 views
Month 42: 37 views
Month 43: 21 views
Month 44: 24 views
Month 45: 18 views
Month 46: 42 views
Month 47: 28 views
Month 48: 31 views
Month 49: 42 views
Month 50: 20 views
Month 51: 22 views
Month 52: 38 views
Month 53: 23 views
Month 54: 40 views
Month 55: 41 views
Month 56: 21 views
Month 57: 34 views
Month 58: 29 views
Month 59: 25 views
Month 60: 34 views
Month 61: 34 views
Month 62: 30 views
Month 63: 11 views
Month 64: 31 views
Month 65: 20 views
Month 66: 42 views
Month 67: 31 views
Month 68: 19 views
Month 69: 20 views
Month 70: 25 views
Month 71: 25 views
Month 72: 35 views
Month 73: 32 views
Month 74: 42 views
Month 75: 36 views
Month 76: 43 views
Month 77: 34 views
Month 78: 37 views
Month 79: 29 views
Month 80: 38 views
Month 81: 39 views
Month 82: 40 views
Month 83: 34 views
Month 84: 30 views
Month 85: 34 views
Month 86: 47 views
Month 87: 42 views
Month 88: 21 views
Month 89: 24 views
Month 90: 16 views
Month 91: 25 views
Month 92: 33 views
Month 93: 22 views
Month 94: 17 views
Month 95: 40 views
Month 96: 31 views
Month 97: 31 views
Month 98: 29 views
Month 99: 32 views
Month 100: 38 views
Month 101: 33 views
Month 102: 27 views
Month 103: 30 views
Month 104: 28 views
Month 105: 26 views
Month 106: 28 views
Month 107: 30 views
Month 108: 20 views
Month 109: 27 views
Month 110: 33 views
Month 111: 32 views
Month 112: 22 views
Month 113: 21 views
Month 114: 39 views
Month 115: 38 views
Month 116: 43 views
Month 117: 36 views
Month 118: 87 views
Month 119: 54 views
Month 120: 38 views

Total Views: 3929

Total Downloads: 2022

2026 Trends

Our website is actively being updated, and changes may occur frequently. Please clear your browser cache if needed. For feedback or error reporting, please email [email protected]