Naslov
Anti-inflammatory properties of bone morphogenetic protein-7 might be beneficial in the treatment of inflammatory bowel disease

Autori
Marić, Ivana ; Poljak, Ljiljana ; Zoričić, Sanja ; Bobinac, Dragica

Vrsta, podvrsta i kategorija rada
Sažeci sa skupova, sažetak, znanstveni

Izvornik
Abstracts of the 29th European Symposium on Calcified Tissues ; u: Calcified Tissue International / Civitelli, Roberto ; Hruska, Keith ; Ralston, H. Stuart - New York (NY) : Springer, 2002, 270-270

Skup
European Symposium on Calcified Tissues (29 ; 2002)

Mjesto i datum
Zagreb, Hrvatska, 25.05.2002. - 29.05.2002

Vrsta sudjelovanja
Poster

Vrsta recenzije
Međunarodna recenzija

Ključne riječi
inflammatory bowel disease; cytokines; bone morphogenetic protein-7; anti-inflammatory response

Sažetak
Abundant expression of bone morphogenetic protein-7 (BMP-7) in the developing intestine and the association of chronic intestinal inflamamtion and the malignant intestinal cell phenotype with alterations in the SMAD signaling pathway argue for an important unrecognized role of BMPs in the pathophsyiology of the gut. In the present study we have evulated the effect of recombinant human BMP-7 for the treatment of trinitrobenzenesulfonic (TNB) acid induced inflamamtory bowel disease (IBD) in rats.Bioavailability studies in normal rats indicate that circulating iodinated BMP-7 declines with a half-life of 30 min upon systemic administration.A significant portion of 3.6% and 4.6% of the administered BMP-7 dose/g tissue is targeted for BMP-7 receptors in the stomach and ileum, respectively. We show that BMP-7 treated animals developed a much less severe form of colitis determined by preserved macroscopic appearance, normal body weight, less diarrhea and rectal bleeding, lack of ulcers and adhesions and reduced histological damage score when administered 1.5h before or 24h after colitis induction. Rats were killed 2, 5, 10, 14 and 30 days following TNB administration.Histochemical and molecular analyses demonstrate that BMP-7: a) preserves microarchitecture of colon tissue, b) suppresses and prevents the accumulation of neutrophils, c) stimulates wound repair and modulates mucosal immunity by downregulating TNF-alpha and TGF-beta, and by inhibiting IL-6 expression, d) modulates the expression of BMP-7 specific receptor, ALK-2 molecule. Collectively, these results suggest that BMP-7 prevents and restores the loss of gut function associated with TNB induced colitis by a mechanism which makes it unique among many other agents reported to be benefical in the treatment of IBD.

Izvorni jezik
Engleski

Znanstvena područja
Temeljne medicinske znanosti

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