PMID- 33196322
OWN - NLM
STAT- MEDLINE
DCOM- 20210201
LR  - 20240226
IS  - 1522-1466 (Electronic)
IS  - 1522-1466 (Linking)
VI  - 320
IP  - 1
DP  - 2021 Jan 1
TI  - Connexin43 is differentially distributed within renal vasculature and mediates 
      profibrotic differentiation in medullary fibroblasts.
PG  - F17-F30
LID - 10.1152/ajprenal.00453.2020 [doi]
AB  - Connexins (Cxs) form gap junctions for intercellular exchange of inorganic ions 
      and messenger molecules. In the kidney, Cxs play essential roles within its 
      compartments, but data on the precise cellular localization and cell type-related 
      function of their isoforms are scarce. We tested whether Cx43 distribution is 
      restricted to vascular and interstitial cells and whether medullary fibroblasts 
      express Cx43 to coordinate profibrotic signaling. Confocal immunofluorescence 
      techniques, ultrastructural labeling, and functional experiments in cell culture 
      were performed. Cx43 was chiefly expressed in the vasculature but was absent from 
      tubular epithelia. All arterial, arteriolar, and lymphatic endothelia showed 
      continuous Cx43 signal along their borders. In the inner medulla, only the 
      interstitium showed Cx43 signals, which were assigned to fibroblasts and their 
      processes. Cultured Cx43-expressing medullary fibroblasts served to study the 
      role of gap junctions in a profibrotic context. In a dye spreading assay, 
      Cx43-sensitive diffusion of Lucifer yellow was dependent on gap junctional 
      passage. The addition of transforming growth factor-beta1 (5 ng/mL for 48 h) 
      activated Cx43 biosynthesis and caused Cx43-sensitive transformation of the 
      fibroblasts into a myofibroblast phenotype. This suggested that Cx43 gap 
      junctional channels enable the coordination of profibrotic signaling between 
      cells of the medullary interstitium. In summary, we demonstrate the presence of 
      Cx43-expressing gap junctions within the two major renal compartments, the 
      vasculature and interstitium. Endothelial Cx43 likely provides functions of an 
      earlier-defined "electrical syncytium" within the vascular wall. Additionally, 
      Cx43 facilitates profibrotic signaling between medullary interstitial 
      fibroblasts.
FAU - Xu, Yan
AU  - Xu Y
AD  - Department of Anatomy, Charite-Universitatsmedizin Berlin, Berlin, Germany.
FAU - Hu, Junda
AU  - Hu J
AD  - Department of Anatomy, Charite-Universitatsmedizin Berlin, Berlin, Germany.
FAU - Yilmaz, Duygu Elif
AU  - Yilmaz DE
AD  - Department of Anatomy, Charite-Universitatsmedizin Berlin, Berlin, Germany.
FAU - Bachmann, Sebastian
AU  - Bachmann S
AD  - Department of Anatomy, Charite-Universitatsmedizin Berlin, Berlin, Germany.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20201116
PL  - United States
TA  - Am J Physiol Renal Physiol
JT  - American journal of physiology. Renal physiology
JID - 100901990
RN  - 0 (Connexin 43)
RN  - 0 (GJA1 protein, human)
RN  - 0 (GJA1 protein, mouse)
RN  - 0 (Gja1 protein, rat)
SB  - IM
MH  - Animals
MH  - Cell Communication
MH  - *Cell Differentiation
MH  - Cell Line
MH  - Connexin 43/*metabolism
MH  - Endothelial Cells/*metabolism/ultrastructure
MH  - Fibroblasts/*metabolism/ultrastructure
MH  - Fibrosis
MH  - Gap Junctions/metabolism/ultrastructure
MH  - Humans
MH  - Kidney Medulla/*blood supply/*metabolism/ultrastructure
MH  - Male
MH  - Mice, Inbred C57BL
MH  - Myofibroblasts/metabolism/ultrastructure
MH  - Phenotype
MH  - Rats, Wistar
MH  - Mice
MH  - Rats
OTO - NOTNLM
OT  - connexon
OT  - fibrosis
OT  - intima
OT  - renomedullary interstitial cell
OT  - transforming growth factor-beta1
EDAT- 2020/11/17 06:00
MHDA- 2021/02/02 06:00
CRDT- 2020/11/16 14:47
PHST- 2020/11/17 06:00 [pubmed]
PHST- 2021/02/02 06:00 [medline]
PHST- 2020/11/16 14:47 [entrez]
AID - 10.1152/ajprenal.00453.2020 [doi]
PST - ppublish
SO  - Am J Physiol Renal Physiol. 2021 Jan 1;320(1):F17-F30. doi: 
      10.1152/ajprenal.00453.2020. Epub 2020 Nov 16.