During spermatogenesis, extensive restructuring of blood–testis barrier takes place to facilitate the migration of preleptotene/leptotene spermatocytes from the basal to the adluminal compartment in the seminiferous epithelium. However, the biochemical mechanisms involved in this event remain elusive. Recent studies have shown that pro-inflammatory cytokine TNFα (tumour necrosis factor α) plays a crucial role in this event by inhibiting the expression of tight junction proteins in Sertoli cells. In the present study, we sought to examine the detailed mechanism on how TNFα affects the expression of CLMP (coxsackie- and adenovirus-receptor-like membrane protein), a newly identified tight junction transmembrane protein, in the testis. Addition of TNFα (10 ng/ml) to Sertoli cell culture (TM4 cells) significantly reduced the steady-state CLMP mRNA and protein levels. In an mRNA stability assay, it was shown that the rate of CLMP mRNA degradation was significantly increased when cells treated with TNFα were compared with vehicle. Blockage of the JNK (c-Jun N-terminal kinase) signalling pathway by SP600125 significantly abolished the TNFα-mediated destabilization of CLMP mRNA. Activation of the JNK signalling pathway by TNFα up-regulated the expression of an RNA-binding protein, TTP (tristetraprolin). TTP was present in the RNA–protein complex in the RNA EMSA (electrophoretic mobility shift assay) and decreased the CLMP 3′-UTR (untranslated region)-dependent luciferase activity. Taken together, these results suggest that the TNFα-mediated mRNA degradation of the CLMP gene is controlled by TTP through the JNK signalling cascade.
Skip Nav Destination
Article navigation
March 2008
-
Cover Image
Cover Image
- PDF Icon PDF LinkFront Matter
- PDF Icon PDF LinkTable of Contents
- PDF Icon PDF LinkEditorial Board
Research Article|
February 27 2008
Post-transcriptional regulation of CLMP mRNA is controlled by tristetraprolin in response to TNFα via c-Jun N-terminal kinase signalling
Kit-Ling Sze;
Kit-Ling Sze
1School of Biological Sciences, The University of Hong Kong, Pokfulam, Hong Kong
Search for other works by this author on:
Wing-Yee Lui;
Wing-Yee Lui
1School of Biological Sciences, The University of Hong Kong, Pokfulam, Hong Kong
Search for other works by this author on:
Will M. Lee
Will M. Lee
1
1School of Biological Sciences, The University of Hong Kong, Pokfulam, Hong Kong
1To whom correspondence should be addressed (email hrszlwm@hku.hk).
Search for other works by this author on:
Publisher: Portland Press Ltd
Received:
July 09 2007
Revision Received:
November 29 2007
Accepted:
November 30 2007
Accepted Manuscript online:
November 30 2007
Online ISSN: 1470-8728
Print ISSN: 0264-6021
© The Authors Journal compilation © 2008 Biochemical Society
2008
Biochem J (2008) 410 (3): 575–583.
Article history
Received:
July 09 2007
Revision Received:
November 29 2007
Accepted:
November 30 2007
Accepted Manuscript online:
November 30 2007
Citation
Kit-Ling Sze, Wing-Yee Lui, Will M. Lee; Post-transcriptional regulation of CLMP mRNA is controlled by tristetraprolin in response to TNFα via c-Jun N-terminal kinase signalling. Biochem J 15 March 2008; 410 (3): 575–583. doi: https://doi.org/10.1042/BJ20070901
Download citation file:
Sign in
Don't already have an account? Register
Sign in to your personal account
You could not be signed in. Please check your email address / username and password and try again.
Captcha Validation Error. Please try again.