. "1"^^ . "The outcome of the project are 4 publication with very good IF factor. In addition, authors generated 4 gene modified mice models. Thus, the grant aims have beem properly addressed and authors get appropriate results."@en . . . "The Impact of a Liver-Specific Deficiency of Growth Factor Sheddase ADAM10 on Liver Development and Pathology"@en . . "2014-07-01+02:00"^^ . . "The importance of epidermal growth factor receptor ligands in liver regeneration, inflammation, and fibrosis has been well established; however, the role of ADAM10, one of their main sheddases, is unknown. At least two ADAM10 substrates, TGFa and EGF, are responsible for the second phase of liver regeneration, the progression of hepatocytes to G1/S-phase. Moreover, ADAM10 is involved in shedding of cMet and as such it could control HGF signaling. We will analyze the role of ADAM10 in liver regeneration, chemically induced inflammation and fibrosis in mice with liver-specific deletion of ADAM10 in vivo. As function of ADAM10 partially overlaps with ADAM17, double liver-specific KO mice will be created to characterize their cooperation and redundancy. ADAM10 transgenic mice with inducible liver-specific expression will be generated to elucidate the role of ADAM10 without affecting the level of proinflamatory and profibrotic cytokines. Complementary in vitro experiments will focus on the role of ADAM10 in interactions among main liver cellular components."@en . "6"^^ . "ADAM10 ADAM17 liver fibrosis liver regeneration sheddase transgenic mouse"@en . "GAP303/10/2044" . . "2013-06-07+02:00"^^ . "6"^^ . . . "Vliv jatern\u011B-specifick\u00E9 delece ADAM10, prote\u00E1zy uvol\u0148uj\u00EDc\u00ED r\u016Fstov\u00E9 faktory, na v\u00FDvoj a patologii jater" . "D\u016Fle\u017Eitost ligand\u016F receptoru epiderm\u00E1ln\u00EDho r\u016Fstov\u00E9ho faktoru ve fyziologick\u00FDch a patologick\u00FDch procesech jater je detailn\u011B charakterizov\u00E1na, nicm\u00E9n\u011B, \u00FAloha jedn\u00E9 ze dvou protein\u00E1z, kter\u00E9 tyto ligandy uvol\u0148uj\u00ED, ADAM10, nebyla v t\u011Bchto procesech zat\u00EDm zkoum\u00E1na. Nejm\u00E9n\u011B dva ze substr\u00E1t\u016F ADAM10, TGFa and EGF, jsou zodpov\u011Bdn\u00E9 za druhou f\u00E1zi regenera\u010Dn\u00EDho procesu jater \u2013 tj. za p\u0159echod hepatocyt\u016F\u00A0 z f\u00E1ze G1 do f\u00E1ze G1/S.\u00A0 ADAM10 se tak\u00E9 pod\u00EDl\u00ED na uvol\u0148ov\u00E1n\u00ED dal\u0161\u00EDch faktor\u016F v\u00FDznamn\u00FDch pro funkci jater;\u00A0 nap\u0159. uvol\u0148ov\u00E1n\u00EDm cMet, receptoru hepatick\u00E9ho r\u016Fstov\u00E9ho faktoru (HGF). Na\u0161im c\u00EDlem je ur\u010Dit \u00FAlohu ADAM10 p\u0159i regeneraci, z\u00E1n\u011Btu a v\u00FDvoji fibr\u00F3zy v j\u00E1trech pomoc\u00ED my\u0161\u00EDho modelu, kter\u00FD je kondicion\u00E1ln\u011B deficientn\u00ED pro gen protein\u00E1zy ADAM10 v j\u00E1trech. Funkce protein\u00E1zy ADAM10 se \u010D\u00E1ste\u010Dn\u011B p\u0159ekr\u00FDv\u00E1 s funkc\u00ED protein\u00E1zy ADAM17. Aby bylo mo\u017Eno charakterizovat\u00A0 kooperaci a redundanci fukc\u00ED t\u011Bchto protein\u00E1z, budu tyto dv\u011B mutantn\u00ED linie zk\u0159\u00ED\u017Eeny, aby vznikla linie s dvojitou deficienc\u00ED v j\u00E1trech. Bude tak\u00E9 vytvo\u0159ena ADAM10-transgenn\u00ED my\u0161 se specifickou a indukovatelnou jatern\u00ED expresi t\u00E9to protein\u00E1zy, aby mohly b\u00FDt zkoum\u00E1na jej\u00ED role bez vlivu z\u00E1n\u011Btliv\u00FDch faktor\u016F indukuj\u00EDc\u00EDch fibr\u00F3zu." . . . . . . . "\u0158e\u0161en\u00ED projektu lze pova\u017Eovat za vynikaj\u00EDc\u00ED s p\u0159ihl\u00E9dnut\u00EDm k n\u00E1ro\u010Dnosti t\u00E9matu (mimo jin\u00E9 vytvo\u0159en\u00ED 4 geneticky modifikovan\u00FDch my\u0161\u00EDch kmen\u016F), velikosti t\u00FDmu, exkluzivit\u011B dedikac\u00ED i d\u00E9lce \u0159e\u0161en\u00ED projektu."@cs . "0"^^ . "http://www.isvav.cz/projectDetail.do?rowId=GAP303/10/2044"^^ . . . . "2010-01-01+01:00"^^ . "2013-12-31+01:00"^^ . . "0"^^ .