Article (Scientific journals)
ADAM metallopeptidase with thrombospondin type 1 motif 2 inactivation reduces the extent and stability of carbon tetrachloride-induced hepatic fibrosis in mice
Kesteloot, Frédéric; Desmoulière, Alexis; Leclercq, Isabelle et al.
2007In Hepatology, 46 (5), p. 1620-1631
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Abstract :
[en] ADAMTS2 belongs to the "ADAM metallopeptidase with thrombospondin type I motif" (ADAMTS) family. Its primary function is to process collagen type I, II, III, and V precursors into mature molecules by excising the aminopropeptide. This process allows the correct assembly of collagen molecules into fibrils and fibers, which confers to connective tissues their architectural structure and mechanical resistance. To evaluate the impact of ADAMTS2 on the pathological accumulation of extracellular matrix proteins, mainly type I and III collagens, we evaluated carbon tetrachloride-induced liver fibrosis in ADAMTS2-deficient (TS2(-/-)) and wild-type (WT) mice. A single carbon tetrachloride injection caused a similar acute liver injury in deficient and WT mice. A chronic treatment induced collagen deposition in fibrous septa that were made of thinner and irregular fibers in TS2(-/-) mice. The rate of collagen deposition was slower in TS2(-/-) mice, and at an equivalent degree of fibrosis, the resorption of fibrous septa was slightly faster. Most of the genes involved in the development and reversion of the fibrosis were similarly regulated in TS2(-/-) and NW mice. Conclusion: These data indicate that the extent of fibrosis is reduced in TS2(-/-) mice in comparison with their WT littermates. Inhibiting the maturation of fibrillar collagens may be a beneficial therapeutic approach to interfering with the development of fibrotic lesions.
Disciplines :
Gastroenterology & hepatology
Author, co-author :
Kesteloot, Frédéric ;  Université de Liège - ULiège > Département des sciences biomédicales et précliniques > Protéines et glycoprot. de matr.extracell. et membran.basal.
Desmoulière, Alexis;  Université Victor Segalen Bordeaux 2 - Bordeaux, France > Institut National de la Santé et de la Recherche Médicale E0362 > Groupe de Recherches pour l’Etude du Foie
Leclercq, Isabelle;  Université Catholique de Louvain - UCL > Gastroenterology Unit
Thiry, Marc  ;  Université de Liège - ULiège > Département des sciences de la vie > Biologie cellulaire
Arrese Estrada, Jorge ;  Université de Liège - ULiège > Département des sciences biomédicales et précliniques > Anatomie et cytologie pathologiques
Prockop, Darwin J;  Tulane University Health Science Center - New Orleans, LA > Center for Gene Therapy
Lapière, Charles M;  Université de Liège - ULiège > Département des sciences biomédicales et précliniques > Protéines et glycoprot. de matr.extracell. et membran.basal.
Nusgens, Betty ;  Université de Liège - ULiège > Département des sciences biomédicales et précliniques > Département des sciences biomédicales et précliniques
Colige, Alain ;  Université de Liège - ULiège > Département des sciences biomédicales et précliniques > Protéines et glycoprot. de matr.extracell. et membran.basal.
Language :
English
Title :
ADAM metallopeptidase with thrombospondin type 1 motif 2 inactivation reduces the extent and stability of carbon tetrachloride-induced hepatic fibrosis in mice
Publication date :
November 2007
Journal title :
Hepatology
ISSN :
0270-9139
eISSN :
1527-3350
Publisher :
John Wiley & Sons, Hoboken, United States - New Jersey
Volume :
46
Issue :
5
Pages :
1620-1631
Peer reviewed :
Peer Reviewed verified by ORBi
Available on ORBi :
since 09 March 2009

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