PKCδ as a regulator for TGF-β-stimulated connective tissue growth factor production in human hepatocarcinoma (HepG2) cells

2013 ◽  
Vol 456 (1) ◽  
pp. 109-118 ◽  
Author(s):  
Su Jin Lee ◽  
Jeong Han Kang ◽  
Soo Young Choi ◽  
Oh-Shin Kwon

In the present study, we demonstrated that PKCδ-stimulated RhoA/ROCK activation resulted in a reduction in PPM1A, thereby up-regulating Smad-dependent gene induction for extended periods. These findings indicated that PKCδ plays a critical role in TGF-β1-induced CTGF production in HepG2 cells.

Oral Oncology ◽  
2009 ◽  
Vol 45 (9) ◽  
pp. e99-e105 ◽  
Author(s):  
Yi-Ting Deng ◽  
Hsin-Ming Chen ◽  
Shih-Jung Cheng ◽  
Chun-Pin Chiang ◽  
Mark Yen-Ping Kuo

2001 ◽  
Vol 108 (2) ◽  
pp. 241-250 ◽  
Author(s):  
Richard Stratton ◽  
Xu Shiwen ◽  
Giorgia Martini ◽  
Alan Holmes ◽  
Andrew Leask ◽  
...  

2011 ◽  
Vol 441 (1) ◽  
pp. 499-510 ◽  
Author(s):  
Helen C. O'Donovan ◽  
Fionnuala Hickey ◽  
Derek P. Brazil ◽  
David H. Kavanagh ◽  
Noelynn Oliver ◽  
...  

The critical involvement of TGF-β1 (transforming growth factor-β1) in DN (diabetic nephropathy) is well established. However, the role of CTGF (connective tissue growth factor) in regulating the complex interplay of TGF-β1 signalling networks is poorly understood. The purpose of the present study was to investigate co-operative signalling between CTGF and TGF-β1 and its physiological significance. CTGF was determined to bind directly to the TβRIII (TGF-β type III receptor) and antagonize TGF-β1-induced Smad phosphorylation and transcriptional responses via its N-terminal half. Furthermore, TGF-β1 binding to its receptor was inhibited by CTGF. A consequent shift towards non-canonical TGF-β1 signalling and expression of a unique profile of differentially regulated genes was observed in CTGF/TGF-β1-treated mesangial cells. Decreased levels of Smad2/3 phosphorylation were evident in STZ (streptozotocin)-induced diabetic mice, concomitant with increased levels of CTGF. Knockdown of TβRIII restored TGF-β1-mediated Smad signalling and cell contractility, suggesting that TβRIII is key for CTGF-mediated regulation of TGF-β1. Comparison of gene expression profiles from CTGF/TGF-β1-treated mesangial cells and human renal biopsy material with histological diagnosis of DN revealed significant correlation among gene clusters. In summary, mesangial cell responses to TGF-β1 are regulated by cross-talk with CTGF, emphasizing the potential utility of targeting CTGF in DN.


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