Title Izražaj paneksina 1 tijekom razvoja bubrega i prognostički značaj u dijabetičkoj nefropatiji
Title (english) Pannexin 1 expression during kidney development and prognostic significance in diabetic nephropathy
Author Ivo Jeličić
Mentor Natalija Filipović (mentor)
Committee member Dragan Ljutić (predsjednik povjerenstva)
Committee member Snježana Mardešić (član povjerenstva)
Committee member Snježana Tomić (član povjerenstva)
Granter University of Split School of Medicine Split
Defense date and country 2023-03-08, Croatia
Scientific / art field, discipline and subdiscipline BIOMEDICINE AND HEALTHCARE Clinical Medical Sciences Internal Medicine
Universal decimal classification (UDC ) 616 - Pathology. Clinical medicine
Abstract Paneksini su glikoproteini koji formiraju transmembranske kanale velikog promjera putem kojih se otpušta ATP u izvanstanični milje. Na taj način sudjeluju u purinergičkoj parakrinoj komunikaciji između stanica te imaju važnu ulogu u različitim fiziološkim i patološkim procesima. Dijabetička nefropatija najčešći je uzročnik kroničnog bubrežnog zatajenja a njena patofiziologija i dalje nije potpuno jasna. Sve veći broj novijih studija ukazuje na ulogu izravne komunikacije između stanica i parakrinog ATP-a u patofiziologiji DN. U ovoj studiji istražena je glomerularna i tubularna ekspresija Panx1 u bolesnika sa šećernom bolešću tipa 2 i kontrolne skupine te korelacija sa serumskim kreatininom kao pokazateljem bubrežne funkcije. Nađena je značajna pozitivna korelacija između ekspresije Panx1 u glomerulima i kreatinina u serumu, koja je bila izraženija u podskupini bolesnika s dijabetesom, a nije nađena izolirano u skupini bez dijabetesa. Naši podaci sugeriraju da je glomerularna ekspresija Panx1 potencijalni pokazatelj pogoršanja bubrežne funkcije u bolesnika s dijabetesom tipa 2. S obzirom da do sada nema objavljenih podataka o ulozi Panx1 u razvoju bubrega, također je istražena ekspresija Panx1 u različitim fazama embrionalnog i ranog fetalnog razvoja. U 6. tjednu embrionalnog razvoja pronađena je ekspresija Panx1 u mezonefričkim glomerulima i mezonefričkim tubulima. Na prijelazu iz 6. u 7. tjedan embrionalnog razvoja, Panx1 imunoreaktivnost je nađena u mezonefričkim tubulima i mezonefričkom kanalu, kao i u metanefričkom pupoljku uretera i čašicama. U 7. tjednu embrionalnog razvoja, snažna Panx1 ekspresija primijećena je u mokraćovodnom pupoljku u metanefrosu, dok nije pronađena Panx1 imunoreaktivnost u metanefričkoj čašici. U 8. tjednu embrionalnog razvoja, ekspresija Panx1 također je pronađena u mokraćovodnom pupoljku u metanefrosu kao i u bubrežnom mjehuriću i nefronu u obliku zareza, te u epitelnim stanicama Bowmanove kapsule. Ekspresija Panx1 pronađena je u ranoj fazi u paramezonefričkom kanalu i u mezonefričkom kanalu, te se smanjivala prema 8. tjednu. Tijekom 6-10. tjedna kolokalizacija Panx1 s aSMA pronađena je u krvnim žilama u razvoju. U postnatalnom bubregu, jaka imunoreaktivnost Panx1 bila je prisutna u stanicama medularnog i kortikalnog sabirnog kanalića, stanicama koje proizvode renin i proksimalnim tubulima. Vrlo slaba Panx1 imunoreaktivnost pronađena je u određenim distalnim stanicama tubula i u silaznim tankim krakovima Henleove petlje. Imunoreaktivnost Panx1 također je pronađena u podocitima (obilježenih nefrinom). Panx1 nije bio kolokaliziran s aSMA imunoreaktivnošću u žilama postnatalnog ljudskog bubrega, ali je bio prisutan u endotelu. Prostorno-vremenska ekspresija Panx1 tijekom ranih faza razvoja ljudskog bubrega podržava njegovu moguću ulogu u procesima stanične diferencijacije, migracije i pozicioniranja u razvoju ljudskog bubrega.
Abstract (english) Pannexins are glycoproteins that form large diameter transmembrane channels through which ATP is released into the extracellular environment. In this way, they are involved in purinergic paracrine communication between cells and play an important role in various physiological and pathological processes. Diabetic nephropathy is the most common cause of chronic renal failure, and its pathophysiology is still not fully understood. A growing number of recent studies point to the role of direct communication between cell and paracrine ATP in the pathophysiology of DN. In this study, glomerular and tubular expression of Panx1 in patients with type 2 diabetes and control groups and its correlation with serum creatinine as an indicator of renal function were investigated. A significant positive correlation was found between glomerular Panx1 expression and serum creatinine, which was pronounced in the subgroup of patients with diabetes and was not found in isolation in the group without diabetes. Our data suggest that glomerular Panx1 expression is a potential indicator of worsening renal function in patients with type 2 diabetes. In the absence of published data on the role of Panx1 in kidney development, the expression of Panx1 at different stages of embryonic and early fetal development was also investigated. At week 6 of embryonic development, Panx1 expression was found in mesonephric glomeruli and mesonephric tubules. At the transition from the 6th to the 7th week of embryonic development, Panx1 immunoreactivity was found in the mesonephric tubules and the mesonephric duct, as well as in the metanephric ureteric bud and ampullae. At week 7 of embryonic development, strong Panx1 expression was observed in the ureteric bud in the metanephros, whereas no Panx1 immunoreactivity was found in the metanephric cup. At week 8 of embryonic development, Panx1 expression was also detected in the ureteric bud in the metanephros as well as in the renal vesicle and comma-shaped nephron and in the epithelial cells of Bowman's capsule. Expression of Panx1 was found in the paramesonephric duct and mesonephric duct in the early phase and it diminished toward the 8th week. In the 6th to 10th week, colocalization of Panx1 with aSMA was detected in developing blood vessels. In the postnatal kidney, strong Panx1 immunoreactivity was present in medullary and cortical collecting duct cells, renin-producing cells, and proximal tubules. Very weak Panx1 immunoreactivity was found in certain distal tubule cells and in the descending thin limbs of the loop of Henle. Panx1 immunoreactivity was also found in podocytes (labelled with nephrin). Panx1 was not colocalized with aSMA immunoreactivity in postnatal human kidney vessels but was present in the endothelium. The spatiotemporal expression of Panx1 at early stages of human kidney development argues for its possible role in the processes of cell differentiation, migration, and positioning in human kidney development.
Keywords
bubreg
paneksin 1
dijabetičke nefropatije
Keywords (english)
Kidney
pannexin 1
Diabetic Nephropathies
Language croatian
URN:NBN urn:nbn:hr:171:604482
Study programme Title: Obtaining a doctorate of science outside of doctoral studies Study programme type: university Study level: postgraduate Academic / professional title: doktor/doktorica znanosti (doktor/doktorica znanosti)
Type of resource Text
File origin Born digital
Access conditions Open access
Terms of use
Created on 2023-04-03 10:42:27