Matrilysins-1 and -2 (MMP-7 and -26) and metalloelastase (MMP-12), unlike MMP-19, are up-regulated in necrotizing enterocolitis.
OBJECTIVE
Necrotizing enterocolitis (NEC) is the most common gastrointestinal disease of premature infants characterized histologically by extensive tissue injury and inflammation. Matrix metalloproteinases (MMP) are involved in tissue remodeling and cell migration, both being important aspects of inflammatory disease. The aim of this study was to investigate whether MMPs play a role in the pathogenesis of NEC.


METHODS
Expression of MMP-1, -7, -9, -10, -12, -19 and -26 was studied using in situ hybridization/immunohistochemistry in samples intestinal tissue removed from 15 patients with NEC; in 7 of them control samples were obtained at closure of stomas. Six intestinal samples from patients with intestinal atresia and four samples of necrosis were also included in the material examined. Laminin-5 was immunostained to find migrating enterocytes and cytokeratin to delineate mucosal epithelium.


RESULTS
MMP-7 protein was upregulated in the epithelium of 12/18 NEC samples. MMP-26 was induced in stromal cells of 12/17 NEC specimens. Stromal expression was found for MMP-1 and -12 mRNAs in 7/18 samples. MMP-1 was also detected in the epithelium of regenerating areas. Both NEC and stoma samples expressed MMP-9 in inflammatory cells. Epithelial MMP-19 was downregulated in NEC.


CONCLUSIONS
Our results suggest that several MMPs may be major factors in tissue destruction and remodeling in NEC. Targeted inhibition of matrilysins, using synthetic MMP inhibitors or blockers of their signal transduction pathways, may represent a novel therapeutic option for the treatment of intestinal inflammation associated with NEC.
Bister
Ville
V
Department of Dermatology, Helsinki University Central Hospital, Helsinki, Finland.
Salmela
Mikko T
MT
Heikkilä
Päivi
P
Anttila
Annaleena
A
Rintala
Risto
R
Isaka
Keichi
K
Andersson
Sture
S
Saarialho-Kere
Ulpu
U
D016022:Case-Control Studies; D020345:Enterocolitis, Necrotizing / Q000209:etiology* / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D007231:Infant, Newborn; D007234:Infant, Premature; D053508:Matrix Metalloproteinase 12; D020783:Matrix Metalloproteinase 7; D020782:Matrix Metalloproteinases / Q000378:metabolism; D053505:Matrix Metalloproteinases, Secreted; D008666:Metalloendopeptidases / Q000378:metabolism*; D015854:Up-Regulation
C410599:MMP26 protein, human; D020782:Matrix Metalloproteinases; D053505:Matrix Metalloproteinases, Secreted; D008666:Metalloendopeptidases; C108362:matrix metalloproteinase 19; C060932:MMP7 protein, human; D020783:Matrix Metalloproteinase 7; C507122:MMP12 protein, human; D053508:Matrix Metalloproteinase 12