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doctoral thesis
Utjecaj dobi i šećerne bolesti tipa 1 na izražaj bjelančevine MutS homolog 2 u bubregu štakora
2023. urn:nbn:hr:171:695338
Babić, Paško
University of Split
School of Medicine

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Babić, P. (2023). Utjecaj dobi i šećerne bolesti tipa 1 na izražaj bjelančevine MutS homolog 2 u bubregu štakora (Doctoral thesis). Split: University of Split, School of Medicine. Retrieved from https://urn.nsk.hr/urn:nbn:hr:171:695338

Babić, Paško. "Utjecaj dobi i šećerne bolesti tipa 1 na izražaj bjelančevine MutS homolog 2 u bubregu štakora." Doctoral thesis, University of Split, School of Medicine, 2023. https://urn.nsk.hr/urn:nbn:hr:171:695338

Babić, Paško. "Utjecaj dobi i šećerne bolesti tipa 1 na izražaj bjelančevine MutS homolog 2 u bubregu štakora." Doctoral thesis, University of Split, School of Medicine, 2023. https://urn.nsk.hr/urn:nbn:hr:171:695338

Babić, P. (2023). 'Utjecaj dobi i šećerne bolesti tipa 1 na izražaj bjelančevine MutS homolog 2 u bubregu štakora', Doctoral thesis, University of Split, School of Medicine, accessed 04 December 2024, https://urn.nsk.hr/urn:nbn:hr:171:695338

Babić P. Utjecaj dobi i šećerne bolesti tipa 1 na izražaj bjelančevine MutS homolog 2 u bubregu štakora [Doctoral thesis]. Split: University of Split, School of Medicine; 2023 [cited 2024 December 04] Available at: https://urn.nsk.hr/urn:nbn:hr:171:695338

P. Babić, "Utjecaj dobi i šećerne bolesti tipa 1 na izražaj bjelančevine MutS homolog 2 u bubregu štakora", Doctoral thesis, University of Split, School of Medicine, Split, 2023. Available at: https://urn.nsk.hr/urn:nbn:hr:171:695338

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Metadata
TitleUtjecaj dobi i šećerne bolesti tipa 1 na izražaj bjelančevine MutS homolog 2 u bubregu štakora
Title (english)Influence of Age and Diabetes Mellitus Type 1 on MSH2 (MutS homolog 2) Expression in a Rat Kidney Tissue
AuthorPaško Babić
MentorBenjamin Benzon (mentor)
Committee memberMerica Glavina Durdov (predsjednik povjerenstva)
Committee memberJoško Božić (član povjerenstva)
Committee memberTatijana Zemunik (član povjerenstva)
GranterUniversity of Split
School of Medicine
Split
Defense date and country2023-06-21, Croatia
Scientific / art field,
discipline and subdiscipline		BIOMEDICINE AND HEALTHCARE
Basic Medical Sciences
Cytology, Histology and Embryology
Universal decimal classification
(UDC)		61 - Medical sciences
Abstract
Uvod: Homeostaza proliferirajućih tkiva ovisi o cjelovitoj DNA molekuli. MSH2 (MutS homolog 2) pripada sustavu gena popravljača pogrešno sparenih baza i aktivan je u više faza staničnoga ciklusa. Neki tumori i neneoplastične bolesti povezane su s ugašenom ili smanjenom aktivnošću MSH2. Na animalnome modelu štakora analiziran je utjecaj starenja i šećerne bolesti tipa 1 na imunohistokemijski izražaj MSH2 u bubregu, a iz humane transkriptomske javno dostupne baze izražaj mRNA MSH2 u karcinomu bubrega. Tvoriva i postupci: U kohorti je 25 štakora podijeljenih u kontrolnu skupinu i u dijabetičnu skupinu kojoj je u drugom mjesecu života strepotozocinom inducirana šećerna bolest tipa 1. Životinje su žrtvovane u dobi od dva, osam, odnosno 14 mjeseci i oformljeno je pet skupina: zdravi štakori stari 2 mj., stari 8 mj. i stari 14. mj., te štakori sa šećernom bolesti tipa 1 stari 8 mj. i stari 14. mj. Preparati bubrežnoga tkiva obojeni su protutijelom na MSH2 indirektnom imunofluorescentnom metodom, mikroskopski analizirani, fotografirani i izražaj MSH2 kvantificiran u ImageJ računalnome programu. Transkriptomska analiza izražaja mRNA MSH2 u humanome karcinomu bubrega učinjena je iz javno dostupnih baza podataka s mrežne usluge Xena. Rezultati: Dob je glavni čimbenik koji utječe na izražaj MSH2 u tkivu bubrega štakora. Učinak dobi na MSH2 prati paraboličnu dinamiku s vrhuncem izražaja u dobi od 8 mjeseci, dok su razine u dobi od 2 i 14 mjeseci slične (p < 0,001). U štakora sa šećernom bolesti tipa 1 starih 14 mjesec značajno je veći izražaj MSH2 nego u zdravih kontrola iste dobi (p = 0,026). Kad se izražaj MSH2 na mRNA razini u uzorcima humanoga karcinoma normalizira na stopu proliferacije izraženu s mRNA Ki-67, niži je u karcinomu nego u zdravome tkivu (p = 0,011). Zaključak: Starija životna dob smanjuje izražaj MSH2 u bubregu, a šećerna bolest povećava. Utvrđen je relativni manjak mRNA MSH2 u karcinomu bubrega u odnosu na zdravo tkivo što upućuje na relativnu MSH2 deficijenciju.
Abstract (english)
Background: Introduction: Homeostasis of proliferating tissues depends on the complete DNA molecule. MSH2 (MutS homolog 2) belongs to the base mismatch repair gene system and is active in several phases of the cell cycle. Some tumors and non-neoplastic diseases are associated with suppressed or reduced MSH2 activity. The influence of aging and type I diabetes on the immunohistochemical expression of MSH2 in the kidney was analyzed using a rat animal model, and MSH2 mRNA expression in kidney cancer from the publicly available human transcriptome database. Methods: To study the influence of age, three groups of healthy rats were formed: 2 months, 8 months and 14 months old. Two groups of diabetic rats were formed: 8 months old and 14 months old. 8-month-old diabetic rats were diabetic for 6 months, similarly 14-month-old diabetic rats were diabetic for 12 months. The expression of MSH2 in the kidney was studied by quantification of immunofluorescence staining. Transcriptomic analysis of MSH2 expression in human renal carcinoma was performed on a publicly available dataset from the Xena platform. Results: Age was identified as a major factor affecting MSH2 expression in the kidney. The effect of age followed a parabolic dynamic, with peak expression at 8 months of age and similar levels at 2 and 14 months of age (p < 0.001). Diabetes had an age-dependent effect, as evidenced by an increase in MSH2 expression in 14-month-old diabetic rats compared to healthy animals (p = 0.026). In an analysis of MSH2 in human kidney cancer from publicly available datasets, MSH2 mRNA normalized to Ki-67 mRNA proliferation rate appears to be lower in cancer than in healthy tissue (p = 0.011). Conclusions: Age affects MSH2 expression in kidneys more than diabetes mellitus. Since aging is a risk factor for renal neoplasia, the reduction of MSH2 in aged rats could represent one of the pro-oncogenic mechanisms of aging.
Keywords
Keywords (english)
Languagecroatian
URN:NBNurn:nbn:hr:171:695338
Study programmeTitle: Biology of Neoplasms
Study programme type: university
Study level: postgraduate
Academic / professional title: doktor/doktorica znanosti, područje biomedicine i zdravstvo (doktor/doktorica znanosti, područje biomedicine i zdravstvo)
Type of resourceText
File originBorn digital
Access conditionsOpen access
Embargo expiration date: 2023-06-22
Terms of useLicence In copyright icon
Created on2023-06-14 06:48:09