PMID- 32471989 OWN - NLM STAT- MEDLINE DCOM- 20201207 LR - 20210529 IS - 2045-2322 (Electronic) IS - 2045-2322 (Linking) VI - 10 IP - 1 DP - 2020 May 29 TI - Spatio-temporal patterning of different connexins in developing and postnatal human kidneys and in nephrotic syndrome of the Finnish type (CNF). PG - 8756 LID - 10.1038/s41598-020-65777-5 [doi] LID - 8756 AB - Connexins (Cxs) are membrane-spanning proteins which enable flow of information important for kidney homeostasis. Changes in their spatiotemporal patterning characterize blood vessel abnormalities and chronic kidney diseases (CKD). We analysed spatiotemporal expression of Cx37, Cx40, Cx43 and Cx45 in nephron and glomerular cells of developing, postnatal kidneys, and nephrotic syndrome of the Finnish type (CNF) by using immunohistochemistry, statistical methods and electron microscopy. During kidney development, strong Cx45 expression in proximal tubules and decreasing expression in glomeruli was observed. In developing distal nephron, Cx37 and Cx40 showed moderate-to-strong expression, while weak Cx43 expression gradually increased. Cx45/Cx40 co-localized in mesangial and granular cells. Cx43 /Cx45 co-localized in podocytes, mesangial and parietal epithelial cells, and with podocyte markers (synaptopodin, nephrin). Different Cxs co-expressed with endothelial (CD31) and VSMC (alpha -SMA) markers in vascular walls. Peak signalling of Cx37, Cx43 and Cx40 accompanied kidney nephrogenesis, while strongest Cx45 signalling paralleled nephron maturation. Spatiotemporal Cxs patterning indicate participation of Cx45 in differentiation of proximal tubules, and Cx43, Cx37 and Cx40 in distal tubules differentiation. CNF characterized disorganized Cx45 expression in proximal tubules, increased Cx43 expression in distal tubules and overall elevation of Cx40 and Cx37, while Cx40 co-localized with increased number of interstitial myofibroblasts. FAU - Kosovic, Ivona AU - Kosovic I AD - Department of Anatomy, Histology and Embryology, School of Medicine, University of Split, Split, Croatia. FAU - Filipovic, Natalija AU - Filipovic N AD - Department of Anatomy, Histology and Embryology, School of Medicine, University of Split, Split, Croatia. FAU - Benzon, Benjamin AU - Benzon B AD - Department of Anatomy, Histology and Embryology, School of Medicine, University of Split, Split, Croatia. FAU - Vukojevic, Katarina AU - Vukojevic K AD - Department of Anatomy, Histology and Embryology, School of Medicine, University of Split, Split, Croatia. AD - Department of Histology and Embryology, School of Medicine, University of Mostar, Mostar, Bosnia and Herzegovina. FAU - Saraga, Marijan AU - Saraga M AD - Department of Paediatrics, University Hospital in Split, School of Medicine, University of Split, Split, Croatia. FAU - Glavina Durdov, Merica AU - Glavina Durdov M AD - Department of Pathology, University Hospital in Split, School of Medicine, University of Split, Split, Croatia. FAU - Bocina, Ivana AU - Bocina I AD - Department of Biology, Faculty of Science, University of Split, Split, Croatia. FAU - Saraga-Babic, Mirna AU - Saraga-Babic M AUID- ORCID: 0000-0002-9776-2532 AD - Department of Anatomy, Histology and Embryology, School of Medicine, University of Split, Split, Croatia. msb@mefst.hr. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20200529 PL - England TA - Sci Rep JT - Scientific reports JID - 101563288 RN - 0 (ACTA2 protein, human) RN - 0 (Actins) RN - 0 (Connexins) RN - 0 (Membrane Proteins) RN - 0 (Microfilament Proteins) RN - 0 (PECAM1 protein, human) RN - 0 (Platelet Endothelial Cell Adhesion Molecule-1) RN - 0 (SYNPO protein, human) RN - 0 (nephrin) SB - IM MH - Actins/biosynthesis/genetics MH - Connexins/*biosynthesis/genetics MH - Gap Junctions/ultrastructure MH - *Gene Expression Regulation, Developmental MH - Gestational Age MH - Humans MH - Infant MH - Kidney/embryology/growth & development/*metabolism/ultrastructure MH - Male MH - Membrane Proteins/deficiency MH - Mesenchymal Stem Cells/metabolism MH - Microfilament Proteins/biosynthesis/genetics MH - Mutation, Missense MH - Nephrotic Syndrome/genetics/*metabolism MH - Organ Specificity MH - Platelet Endothelial Cell Adhesion Molecule-1/biosynthesis/genetics PMC - PMC7260365 COIS- The authors declare no competing interests. EDAT- 2020/05/31 06:00 MHDA- 2020/12/15 06:00 PMCR- 2020/05/29 CRDT- 2020/05/31 06:00 PHST- 2020/02/19 00:00 [received] PHST- 2020/05/06 00:00 [accepted] PHST- 2020/05/31 06:00 [entrez] PHST- 2020/05/31 06:00 [pubmed] PHST- 2020/12/15 06:00 [medline] PHST- 2020/05/29 00:00 [pmc-release] AID - 10.1038/s41598-020-65777-5 [pii] AID - 65777 [pii] AID - 10.1038/s41598-020-65777-5 [doi] PST - epublish SO - Sci Rep. 2020 May 29;10(1):8756. doi: 10.1038/s41598-020-65777-5.