Deoxycholate-Induced Colitis is Markedly Attenuated in Nos2 Knockout Mice in Association with Modulation of Gene Expression Profiles

2007 ◽  
Vol 52 (3) ◽  
pp. 628-642 ◽  
Author(s):  
Harris Bernstein ◽  
Hana Holubec ◽  
Carol Bernstein ◽  
Natalia A. Ignatenko ◽  
Eugene Gerner ◽  
...  
2010 ◽  
Vol 24 (9) ◽  
pp. 1794-1804 ◽  
Author(s):  
Zhilin Liu ◽  
Heng-Yu Fan ◽  
Yibin Wang ◽  
JoAnne S. Richards

Abstract MAPK14 (p38MAPKα) is critical for FSH and prostaglandin E (PGE)2 signaling cascades in granulosa cells (GCs) and cumulus cell-oocyte complexes (COCs) in culture, indicating that this kinase might impact follicular development and COC expansion in vivo. Because Mapk14 knockout mice are embryonic lethal, we generated GC specific Mapk14 knockout mice (Mapk14gc−/−) by mating Mapk14fl/fl and Cyp19-Cre mice. Unexpectedly, the Mapk14gc−/− female mice were fertile. Analyses of gene expression patterns showed that amphiregulin (Areg) and epiregulin (Ereg), two key regulators of ovulation and COC expansion, were up-regulated in the GCs but down-regulated in cumulus cells of the mutant mice in vivo. COCs from the mutant mice expanded and expressed matrix-related genes, if cultured with AREG, but not when cultured with forskolin or PGE2, the latter being a key factor regulating MAPK14 activity in cumulus cells. Conversely, when GCs from the Mapk14gc−/− mice were cultured with forskolin, they produced more Areg and Ereg mRNA than did wild-type GCs. These results indicate that disruption of Mapk14 selectively alters the expression of Areg and other genes in each cell type. Greater AREG and EREG produced by the GCs appears to by-pass and compensate for the critical need for MAPK14 signaling and induction of Areg/Ereg (and hence matrix genes) by PGE2 in cumulus cells of the mutant mice. In conclusion, although MAPK14 is not overtly essential for preovulatory follicle development or events associated with ovulation and luteinization in vivo, it does impact gene expression profiles.


2015 ◽  
Vol 16 (12) ◽  
pp. 28320-28333 ◽  
Author(s):  
Zhenshan Wang ◽  
Yanfen Zhou ◽  
Yingtao Luo ◽  
Jing Zhang ◽  
Yunpeng Zhai ◽  
...  

2005 ◽  
Vol 288 (2) ◽  
pp. 528-544 ◽  
Author(s):  
Olga Barmina ◽  
Martin Gonzalo ◽  
Lauren M. McIntyre ◽  
Artyom Kopp

2012 ◽  
Vol 8 (3) ◽  
pp. 281-287 ◽  
Author(s):  
Ju Yeon Ban ◽  
Hyo Chul Youn ◽  
Hyun-Kyung Park ◽  
Geum-hee Gwak ◽  
Bum Shik Kim

1999 ◽  
Vol 3 (5) ◽  
pp. 249-259 ◽  
Author(s):  
Ally-Khan Somani ◽  
Najwa Esmail ◽  
Katherine A. Siminovitch

Background: Recent advances in the molecular characterization of dermatologic disease have substantively augmented the understanding of the pathogenetic processes underlying disorders of the skin. This new knowledge coupled with progress in gene delivery technologies has paved the way for introducing cutaneous gene therapy into the dermatologic therapeutic armamentorium. Objective: This review article includes an overview of the current strategies for delivery of gene therapy with an emphasis on the potential role of cutaneous gene delivery in the treatment of skin and systemic diseases. Conclusions: Accessibility for gene delivery, clinical evaluation, and topical modulation of gene expression render the skin a very attractive tissue for therapeutic gene delivery. However, there are several key hurdles to be overcome before cutaneous gene therapy becomes a viable clinical option. These include difficulties in inducing sustained expression of the desired gene in vivo, the challenge of targeting genes to long-lived stem cells, and the difficulty in achieving specific and uniform transfer to different compartments of the skin. However, these problems are not insurmountable and will likely be resolved in conjunction with ongoing advances in delineating gene expression profiles and other molecular properties of the skin, strategies for stem cell isolation, and improved approaches to regulating gene delivery and expression. These advances should create the framework for translating the enormous potential of cutaneous gene therapy into the clinical arena and, thereby, substantively improving the management of both cutaneous and systemic disease.


2010 ◽  
Vol 31 (4) ◽  
pp. 606-606
Author(s):  
Zhilin Liu ◽  
Heng-Yu Fan ◽  
Yibin Wang ◽  
JoAnne S. Richards

Abstract MAPK14 (p38MAPKα) is critical for FSH and prostaglandin E (PGE)2 signaling cascades in granulosa cells (GCs) and cumulus cell-oocyte complexes (COCs) in culture, indicating that this kinase might impact follicular development and COC expansion in vivo. Because Mapk14 knockout mice are embryonic lethal, we generated GC specific Mapk14 knockout mice (Mapk14gc−/−) by mating Mapk14fl/fl and Cyp19a1-Cre mice. Unexpectedly, the Mapk14gc−/− female mice were fertile. Analyses of gene expression patterns showed that amphiregulin (Areg) and epiregulin (Ereg), two key regulators of ovulation and COC expansion, were up-regulated in the GCs but down-regulated in cumulus cells of the mutant mice in vivo. COCs from the mutant mice expanded and expressed matrix-related genes, if cultured with AREG, but not when cultured with forskolin or PGE2, the latter being a key factor regulating MAPK14 activity in cumulus cells. Conversely, when GCs from the Mapk14gc−/− mice were cultured with forskolin, they produced more Areg and Ereg mRNA than did wild-type GCs. These results indicate that disruption of Mapk14 selectively alters the expression of Areg and other genes in each cell type. Greater AREG and EREG produced by the GCs appears to by-pass and compensate for the critical need for MAPK14 signaling and induction of Areg/Ereg (and hence matrix genes) by PGE2 in cumulus cells of the mutant mice. In conclusion, although MAPK14 is not overtly essential for preovulatory follicle development or events associated with ovulation and luteinization in vivo, it does impact gene expression profiles.


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