Title Promjene izražaja dipeptidil-peptidaze 8 i 9 u kolitisu
Title (english) CHANGES IN THE EXPRESSION OF DIPEPTIDYL-PEPTIDASE 8 AND 9 IN COLITIS
Author Barbara Franović
Mentor Dijana Detel (mentor)
Committee member Lara Batičić (predsjednik povjerenstva)
Committee member Slađana Bursać (član povjerenstva)
Committee member Dijana Detel (član povjerenstva)
Granter University of Rijeka Faculty of Medicine (Department of Chemistry and Biochemistry) Rijeka
Defense date and country 2020-07-16, Croatia
Scientific / art field, discipline and subdiscipline BIOMEDICINE AND HEALTHCARE Basic Medical Sciences Medical Biochemistry
Abstract UVOD: Ulcerozni kolitis (UK) je jedan od dva patohistološka oblika upalne bolesti crijeva. Predstavlja imunološki posredovanu bolest obilježenu ponavljajućim upalnim procesima koji rezultiraju oštećenjem i gubitkom funkcije crijevne sluznice. Pokazano je da su proteini obitelji dipeptidil-peptidaze (DP)4, posebice, nedovoljno istraženi članovi, DP8 i 9 putem svojih enzimskih i kostimulacijskih učinaka uključeni u modulaciju imunoloških mehanizama te proliferaciju i aktivaciju stanica koji vode
... More k razvoju upalne bolesti crijeva.
CILJ: Cilj je istraživanja ispitati promjene transkripcijske aktivnosti DP8 i 9, signalnog pretvarača i aktivatora transkripcije (STAT)3 i 6 te inducibilne dušične sintetaze (iNOS) na eksperimentalnom modelu UK izazvanog primjenom natrijevog dekstran sulfata (DSS).
MATERIJAL I METODE: Eksperimentalni akutni kolitis je izazvan je u C57BL/6 miševa primjenom 3 % otopine DSS tijekom sedam dana u vodi za piće. Tijekom pokusnog perioda pratio se razvoj i intenzitet kolitisa temeljem promjena kliničkih manifestacija, indeksa aktivnosti bolesti, te lokalnih promjena. Nadalje, pratile su se promjene izražaja DP8 i 9, iNOS te STAT3 i STAT6 na transkripcijskoj razini u tkivu debeloga crijeva tijekom razvoja DSS kolitisa u miša.
REZULTATI: Razvoj upalnog procesa na sistemskoj razini rezultirao je pojavom kliničkih manifestacija, porastom indeksa aktivnosti bolesti i hepatosomatskog indeksa. Na lokalnoj razini, razvoj kolitisa praćen je porastom mikroskopskog indeksa oštećenja sluznice debelog crijeva i skraćenjem debelog crijeva. Trećeg dana pokusnog perioda zabilježen je značajan porast transkripcijske aktivnosti DP8, DP9, STAT3 i iNOS. Značajan porast transkripcijske aktivnosti STAT3 i iNOs zabilježen je i sedmog dana. Izražaj STAT6 gena se tijekom razvoja kolitisa nije mijenjao.
ZAKLJUČAK: Rezultati ukazuju na ulogu ispitivanih proteaza i signalnih molekula u razvoju i progresiji DSS kolitisa. Less
Abstract (english) Introduction. Ulcerative colitis (UC) is one of the two major pathohistological forms of inflammatory bowel disease. It represents an immune mediated disease which is characterized by recurrent episodes of the colon inflammation resulting in damage and loss of the intestinal mucosal function. It has been shown that the proteases dipeptidyl peptidase (DP)4 and recently discovered DP8 and 9 are involved in the modulation of immune mechanisms leading to colitis development as well as in the
... More proliferation and activation of immune cells.
Aim. Considering our previous results and experience, we hypothesized that changes in the expression of DP8 and 9 influence on the colitis development. Therefore, the aim of the research was to investigate the role of DP8 and 9, STAT3 and STAT6, and inducible nitric oxide synthase (iNOS) in the induction and progression of dextran sulfate sodium (DSS)-induced experimental colitis in mice.
Material and Methods. Colitis was induced in C57BL/6 mice by oral administration of 3% solution of DSS. The health status of animals, changes in body weight, and development of clinical symptoms of colitis were monitored during the experimental period. Animals were sacrificed on day 7. Transcriptional expression of the DP8, DP9, STAT3, STAT6, and iNOS in the colonic tissue were evaluated by RT-qPCR.
Results. The development of the colonic inflammation resulted in the appearance of clinical manifestations, an increase in the disease activity index, microscopic damage score and hepatosomatic index. A significant increase in transcriptional activity of DP8, DP9 in the colon was determined on the third day of the experimental period. Likewise, the increase in transcriptional activity of STAT3 and iNOS were determined on the day 3 and 7. Interestingly, development of the colon inflammation has not influenced on the STAT6 gene expression.
Conclusion. The results indicate the importance of investigated proteases and signal molecules in the DSS colitis induction and progression. Less
Keywords
eksperimentalni model
ulerozni kolitis
peptidaze
Keywords (english)
Animals
Ulcerative colitis
dipeptidyl peptidase
Language croatian
URN:NBN urn:nbn:hr:184:493229
Study programme Title: Study of Sanitary Engineering Study programme type: university Study level: graduate Academic / professional title: magistar/magistra sanitarnog inženjerstva (magistar/magistra sanitarnog inženjerstva)
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Created on 2021-01-14 10:40:45