scholarly journals Urothelium-derived Sonic hedgehog promotes mesenchymal proliferation and induces bladder smooth muscle differentiation

2010 ◽  
Vol 79 (4-5) ◽  
pp. 244-250 ◽  
Author(s):  
Mei Cao ◽  
Gregory Tasian ◽  
Ming-Hsien Wang ◽  
Benchun Liu ◽  
Gerald Cunha ◽  
...  
2007 ◽  
Vol 293 (3) ◽  
pp. C1093-C1102 ◽  
Author(s):  
Akihiro Kanematsu ◽  
Aruna Ramachandran ◽  
Rosalyn M. Adam

Hollow organs exposed to pathological stimuli undergo phenotypic modulation characterized by altered expression of smooth muscle contractile proteins and loss of normal function. The molecular mechanisms that regulate smooth muscle differentiation, especially in organs other than the vasculature, are poorly understood. In this study, we describe a role for the GATA-6 transcription factor in regulation of human bladder smooth muscle differentiation. Knockdown of endogenous GATA-6 in primary human bladder smooth muscle cells (pBSMC) led to decreased mRNA levels of the differentiation markers α-smooth muscle actin (α-SMA), calponin, and smooth muscle myosin heavy chain. Similar effects were obtained following downregulation of GATA-6 by forskolin-induced elevation of intracellular cAMP levels. Forskolin treatment of pBSMC abolished recruitment of GATA-6 to the α-SMA promoter in vivo and reduced activity of human α-SMA promoter-directed gene expression by >60%. This inhibitory effect was rescued by enforced expression of wild-type GATA-6 but not by a zinc-finger-deleted mutant, GATA-6-ΔZF, which lacks DNA-binding ability. In silico analysis of a region of the human α-SMA promoter, described previously as a transcriptional enhancer, identified a putative GATA-binding site at position −919/−913. Point mutation of this site in SMA-Luc abrogated GATA-6-induced activation of promoter activity. Together, these results provide the first evidence for a functional role for GATA-6 in regulation of bladder smooth muscle differentiation. In addition, these findings demonstrate that GATA-6 regulates human α-SMA expression via a novel regulatory cis element in the α-SMA promoter-enhancer.


2009 ◽  
Vol 181 (4S) ◽  
pp. 256-256
Author(s):  
Benchun Liu ◽  
Mei Cao ◽  
Gerald R Cunha ◽  
Laurence S Baskin

2010 ◽  
Vol 183 (4S) ◽  
Author(s):  
Gregory Tasian ◽  
Mei Cao ◽  
Gerald Cunha ◽  
Laurence Baskin

2014 ◽  
Vol 6 (1) ◽  
pp. 16-19 ◽  
Author(s):  
Aya Morimoto ◽  
Jun Asai ◽  
Yusuke Wakabayashi ◽  
Satoshi Komori ◽  
Keiji Hanada ◽  
...  

Sign in / Sign up

Export Citation Format

Share Document