Exploring inflammatory and apoptotic signatures in distinct Crohn's disease phenotypes: Way towards molecular stratification of patients and targeted therapy
Nema prikaza
Autori
Stanković, BiljanaDragasević, Sanja
Klaassen, Kristel
Kotur, Nikola
Srzentić Dražilov, Sanja
Zukić, Branka
Sokic Milutinović, Aleksandra
Milovanović, Tamara
Lukić, Snežana
Popović, Dragan
Pavlović, Sonja
Nikčević, Gordana
Članak u časopisu (Objavljena verzija)
Metapodaci
Prikaz svih podataka o dokumentuApstrakt
Background: Crohn's disease (CD) is chronic inflammatory bowel disease with different phenotypic characteristics influencing disease prognosis and therapeutic strategies. The aim of this pilot study was to analyze selected inflammatory and apoptotic markers in non-inflamed and inflamed samples of ileal mucosa of non-stricturing/non-penetrating (NS/NP) and stricturing (S) CD mucosal phenotypes in order to characterize their distinct profiles. Methods: From twenty CD patients (9 NS/NP, 11 S) paired non-inflamed and inflamed ileal biopsies were collected and used for analysis of cytokine (TNF and IL6) and apoptotic (Bcl2, Box, Fas and FasL) genes' expression levels by real-time PCR, while NF kappa B transcriptional potency was assessed by electromobility gel shift assay. Results: Our results demonstrated significant upregulation of TNF and IL6 in inflamed area of both NS/NP (p = 0.03, p = 0.01) and S phenotypes (p = 0.04, p = 0.04), respectively. However, TNF increase was more prominent i...n NS/NP compared to S inflamed mucosa (p = 0.02). Also, level of proapoptotic Box was significantly higher in NS/NP compared to S inflamed mucosa (p = 0.01). Opposing transcription potency of NF kappa B has been detected between two phenotypes: being decreased in NS/NP (p = 0.07) and increased in S (p = 0.1) inflamed compared to non-inflamed mucosa, demonstrating trend towards statistical significance. Conclusions: We found that two distinct CD phenotypes have specific molecular signatures. Obtained results could direct improvement of current and development of new therapeutic strategies based on more specific molecular stratification of CD patients.
Ključne reči:
Mucosal phenotypes / Molecular profiling / Ileal Crohn's diseaseIzvor:
Pathology Research and Practice, 2020, 216, 6Izdavač:
- Elsevier Gmbh, Munich
Finansiranje / projekti:
- Retke bolesti: molekularna patofiziologija, dijagnostički i terapijski modaliteti i socijalni, etički i pravni aspekti (RS-MESTD-Integrated and Interdisciplinary Research (IIR or III)-41004)
- Ministarstvo nauke, tehnološkog razvoja i inovacija Republike Srbije, institucionalno finansiranje - 200042 (Univerzitet u Beogradu, Institut za molekularnu genetiku i genetičko inženjerstvo) (RS-MESTD-inst-2020-200042)
DOI: 10.1016/j.prp.2020.152945
ISSN: 0344-0338
PubMed: 32279918
WoS: 000540160200007
Scopus: 2-s2.0-85083013568
Institucija/grupa
Institut za molekularnu genetiku i genetičko inženjerstvoTY - JOUR AU - Stanković, Biljana AU - Dragasević, Sanja AU - Klaassen, Kristel AU - Kotur, Nikola AU - Srzentić Dražilov, Sanja AU - Zukić, Branka AU - Sokic Milutinović, Aleksandra AU - Milovanović, Tamara AU - Lukić, Snežana AU - Popović, Dragan AU - Pavlović, Sonja AU - Nikčević, Gordana PY - 2020 UR - https://imagine.imgge.bg.ac.rs/handle/123456789/1329 AB - Background: Crohn's disease (CD) is chronic inflammatory bowel disease with different phenotypic characteristics influencing disease prognosis and therapeutic strategies. The aim of this pilot study was to analyze selected inflammatory and apoptotic markers in non-inflamed and inflamed samples of ileal mucosa of non-stricturing/non-penetrating (NS/NP) and stricturing (S) CD mucosal phenotypes in order to characterize their distinct profiles. Methods: From twenty CD patients (9 NS/NP, 11 S) paired non-inflamed and inflamed ileal biopsies were collected and used for analysis of cytokine (TNF and IL6) and apoptotic (Bcl2, Box, Fas and FasL) genes' expression levels by real-time PCR, while NF kappa B transcriptional potency was assessed by electromobility gel shift assay. Results: Our results demonstrated significant upregulation of TNF and IL6 in inflamed area of both NS/NP (p = 0.03, p = 0.01) and S phenotypes (p = 0.04, p = 0.04), respectively. However, TNF increase was more prominent in NS/NP compared to S inflamed mucosa (p = 0.02). Also, level of proapoptotic Box was significantly higher in NS/NP compared to S inflamed mucosa (p = 0.01). Opposing transcription potency of NF kappa B has been detected between two phenotypes: being decreased in NS/NP (p = 0.07) and increased in S (p = 0.1) inflamed compared to non-inflamed mucosa, demonstrating trend towards statistical significance. Conclusions: We found that two distinct CD phenotypes have specific molecular signatures. Obtained results could direct improvement of current and development of new therapeutic strategies based on more specific molecular stratification of CD patients. PB - Elsevier Gmbh, Munich T2 - Pathology Research and Practice T1 - Exploring inflammatory and apoptotic signatures in distinct Crohn's disease phenotypes: Way towards molecular stratification of patients and targeted therapy IS - 6 VL - 216 DO - 10.1016/j.prp.2020.152945 ER -
@article{ author = "Stanković, Biljana and Dragasević, Sanja and Klaassen, Kristel and Kotur, Nikola and Srzentić Dražilov, Sanja and Zukić, Branka and Sokic Milutinović, Aleksandra and Milovanović, Tamara and Lukić, Snežana and Popović, Dragan and Pavlović, Sonja and Nikčević, Gordana", year = "2020", abstract = "Background: Crohn's disease (CD) is chronic inflammatory bowel disease with different phenotypic characteristics influencing disease prognosis and therapeutic strategies. The aim of this pilot study was to analyze selected inflammatory and apoptotic markers in non-inflamed and inflamed samples of ileal mucosa of non-stricturing/non-penetrating (NS/NP) and stricturing (S) CD mucosal phenotypes in order to characterize their distinct profiles. Methods: From twenty CD patients (9 NS/NP, 11 S) paired non-inflamed and inflamed ileal biopsies were collected and used for analysis of cytokine (TNF and IL6) and apoptotic (Bcl2, Box, Fas and FasL) genes' expression levels by real-time PCR, while NF kappa B transcriptional potency was assessed by electromobility gel shift assay. Results: Our results demonstrated significant upregulation of TNF and IL6 in inflamed area of both NS/NP (p = 0.03, p = 0.01) and S phenotypes (p = 0.04, p = 0.04), respectively. However, TNF increase was more prominent in NS/NP compared to S inflamed mucosa (p = 0.02). Also, level of proapoptotic Box was significantly higher in NS/NP compared to S inflamed mucosa (p = 0.01). Opposing transcription potency of NF kappa B has been detected between two phenotypes: being decreased in NS/NP (p = 0.07) and increased in S (p = 0.1) inflamed compared to non-inflamed mucosa, demonstrating trend towards statistical significance. Conclusions: We found that two distinct CD phenotypes have specific molecular signatures. Obtained results could direct improvement of current and development of new therapeutic strategies based on more specific molecular stratification of CD patients.", publisher = "Elsevier Gmbh, Munich", journal = "Pathology Research and Practice", title = "Exploring inflammatory and apoptotic signatures in distinct Crohn's disease phenotypes: Way towards molecular stratification of patients and targeted therapy", number = "6", volume = "216", doi = "10.1016/j.prp.2020.152945" }
Stanković, B., Dragasević, S., Klaassen, K., Kotur, N., Srzentić Dražilov, S., Zukić, B., Sokic Milutinović, A., Milovanović, T., Lukić, S., Popović, D., Pavlović, S.,& Nikčević, G.. (2020). Exploring inflammatory and apoptotic signatures in distinct Crohn's disease phenotypes: Way towards molecular stratification of patients and targeted therapy. in Pathology Research and Practice Elsevier Gmbh, Munich., 216(6). https://doi.org/10.1016/j.prp.2020.152945
Stanković B, Dragasević S, Klaassen K, Kotur N, Srzentić Dražilov S, Zukić B, Sokic Milutinović A, Milovanović T, Lukić S, Popović D, Pavlović S, Nikčević G. Exploring inflammatory and apoptotic signatures in distinct Crohn's disease phenotypes: Way towards molecular stratification of patients and targeted therapy. in Pathology Research and Practice. 2020;216(6). doi:10.1016/j.prp.2020.152945 .
Stanković, Biljana, Dragasević, Sanja, Klaassen, Kristel, Kotur, Nikola, Srzentić Dražilov, Sanja, Zukić, Branka, Sokic Milutinović, Aleksandra, Milovanović, Tamara, Lukić, Snežana, Popović, Dragan, Pavlović, Sonja, Nikčević, Gordana, "Exploring inflammatory and apoptotic signatures in distinct Crohn's disease phenotypes: Way towards molecular stratification of patients and targeted therapy" in Pathology Research and Practice, 216, no. 6 (2020), https://doi.org/10.1016/j.prp.2020.152945 . .