Title Uloga koneksina u međustaničnoj signalizaciji tijekom razvoja ljudskog bubrega i u bubrežnoj
patologiji Title (english) The role of connexin in intercellular signaling during human kidney development and in renal
pathology Author Ivona Kosović Mentor Mirna Saraga-Babić (mentor)Committee member Marijan Šitum (predsjednik povjerenstva)Committee member Snježana Tomić (član povjerenstva)Committee member Tatijana Zemunik (član povjerenstva)Granter University of Split Defense date and country 2021-11-30, Croatia Scientific / art field, BIOMEDICINE AND HEALTHCARE Universal decimal classificationUDC ) 611 - Anatomy Abstract Analiziran je prostorno-vremenski izražaj koneksina (Cx37, Cx40, Cx43 i Cx45), renina,
sinaptopodina, nefrina, CD31 i α-SMA u nefronima i JGA ljudskih prenatalnih zdravih
bubrega, postnatalnih zdravih bubrega te u bubrezima s nefrotskim sindromom Finskog tipa
(CNF). U istraživanju su korištene tehnike dvostruke imunofluorescencije, elektronske
mikroskopije i statističkog mjerenja površina ispod krivulje (AUC) histograma intenziteta
fluorescencije.
Tijekom razvoja bubrega, Cx45 pokazuje jaku ekspresiju u proksimalnim bubrežnim
kanalićima, dok su Cx37 i Cx40 umjereno do jako izraženi u distalnom dijelu nefrona. U
glomerulima, Cx43 i Cx45 ko-lokaliziraju u podocitima, mezangijskim stanicama i
parijetalnim epitelnim stanicama, kao i s biljezima za podocite (sinaptopodin, nefrin). Različiti
koneksini također pokazuju i ko-ekspresiju s endotelnim (CD31) i glatkim-mišićnim (α-SMA)
biljezima u zidu krvnih žila. Cx37, Cx40 i Cx43 imaju najjači intenzitet tijekom razdoblja koje
prati nefrogenezu, dok je najveći intenzitet signala za Cx45 povezan sa sazrijevanjem nefrona.
S obzirom na navedeno prostorno-vremensko uzorkovanje, Cx45 vjerojatno ima ulogu u
diferencijaciji proksimalnih kanalića, a Cx37, Cx40 i Cx43 u diferencijaciji distalnih kanalića.
Tijekom razvoja bubrega, jaka ekspresija Cx40 u JGA postupno opada, dok ekspresija Cx37,
Cx43 i Cx45 raste te se nastavlja i u postnatalnom razdoblju. Bubrezi zahvaćeni CNF-om
pokazuju pojačan izražaj Cx43 u distalnim kanalićima, promijenjeni citoplazmatski raspored
Cx45 u proksimalnim kanalićima te ukupan porast ekspresije Cx40 i Cx37. U CNF-bubrezima
Cx40 ko-lokalizira sa brojnim intersticijskim miofibroblastima. Povećane razine Cx37, Cx43 i
Cx45 u CNF-bubrezima ko-lokaliziraju s reninskim stanicama. Reninske stanice u KBB
uzrokovanom CNF-om javljaju se i u ekstraglomerularnim mezangijskim stanicama, što
ukazuje na njihov povratak u prethodne embrionalne stadije kao posljedica pokušaja
kompenzacije oštećenja bubrežnog tkiva. Cx40 vjerojatno ima važnu ulogu u diferencijaciji
JGA tijekom razvoja bubrega, dok Cx37, Cx43 i Cx45 održavaju pravilnu bubrežnu funkciju
u postnatalnom razdoblju. Naše istraživanje pokazuje važnu ulogu koneksina u nefrogenezi,
diferencijaciji glomerularnih stanica, razvoju krvnih žila i kontroli arterijskog tlaka, kako u
zdravom bubrežnom tkivu tako i u CNF-u.
Abstract (english) Our study analyzed the spatio-temporal patterning of connexins (Cx37, Cx40, Cx43 and C45),
renin, synaptopodin, nephrin, CD31 and α-SMA in the nephron and JGA of developing,
postnatal healthy human kidneys and in the nephrotic syndrome of the Finnish type (CNF). For
data analysis we used double immunofluorescence, electron microscopy and statistical
measuring of area under curve (AUC) of flouorescence intensity histograms.
During kidney development, strong expression of Cx45 characterized proximal tubules, while
Cx37 and Cx40 showed moderate-to-strong expression in developing cells of distal nephron.
In the glomeruli, Cx43 and Cx45 co-localized with markers for podocytes (synaptopodin,
nephrin), with mesangial and parietal epithelial cells. Different connexins also showed coexpression with endothelial (CD31) and VSMC (α-SMA) markers in vascular walls. Cx37,
Cx40 and Cx43 peak in signalling intensity accompanied kidney nephrogenesis, while Cx45
peak signalling associated the nehron maturation. Based on the Cx spatio-temporal patterning,
Cx45 is considered to be important in differentiation of proximal tubules, while Cx37, Cx40
and Cx43 in distal tubules cell differentiation. During kidney development, strong expression
of Cx40 in the JGA gradually decreased, while the expression of Cx37, Cx43 and Cx45
increased and continued in the postnatal period as well. CNF kidneys showed increased Cx43
expression in distal tubules, disorganized cytoplasmic Cx45 expression in proximal tubules,
and overall elevation of Cx40 and Cx37 in kidney tissue. In CNF-kidneys, Cx40 co-localized
with abundant interstitial myofibroblasts. Increased levels of Cx37, Cx43 and Cx45 which colocalized with renin cells also characterized CNF kidneys. Renin cells in chronic kidney disease
(CKD) caused by CNF reappeared in extraglomerular mesangial cells which could imply their
return to embryonic patterning, which is compensatory to the damage of the kidney tissue.
Cx40 probably has a significant role in the formation of the JGA in developing kidneys, while
Cx37, Cx43 and Cx45 take over that role in postnatal maintenance of kidney function. Our
study showed important role of Cxs in nephrogenesis, differentiation of glomerular cells, blood
vessel development and blood pressure control in the healthy kidney tissue and in the CNF.
Keywords
koneksin
bubreg
KKS
α-SMA
CD31
CNF
KBB
Keywords (english)
connexin
kidney
KKS
α-SMA
CD31
CNF
KBB
Language croatian URN:NBN urn:nbn:hr:171:165919 Promotion 2022 Study programme Title: Biology of Neoplasms Type of resource Text File origin Born digital Access conditions Open access Terms of use Created on 2022-01-25 12:22:38
