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. Author manuscript; available in PMC: 2014 Jul 24.
Published in final edited form as: Adv Exp Med Biol. 2012;763:260–280. doi: 10.1007/978-1-4614-4711-5_13

Table 2.

Modulation of connexins and their effects on barrier integrity

Modulation Barrier
Integrity		 Other Observations Tissue or Cell Line
Cx26 Overexpression / Prevent Na+/K+
ATPase inhibitor
ouabain-induced TJ
barrier disruption,
even in the presence of
gap junction blockers
18β-glycyrrhetinic acid
or oleamide; Increase
in Cldn14 expression		 Human transformed
bronchial epithelial
cell line Calu-3150
Overexpression Increase Increase in Cldn4
expression; the increase
in barrier integrity can
be disrupted by oleic
acid, taurocholic acid
and 18α-glycyrrhetinic
acid		 Human colonic cell
line Caco-2151
Ectopic
expression with
epidermis-specific
promoter		 Decrease Disruption of
epidermal barrier
acquisition during
development and
recovery of epidermal
barrier after wounding;
increase in ATP release		 Epidermis of
genetically modified
mice88
Carriers of
R134W Cx26
allele (loss of
function mutant)		 / Increase in epidermal
thickness		 Population study of
human epidermis87
Overexpression
of R134W mutant
(loss of function
mutant)		 / Increase in epidermal
thickness		 Coculture of human
keratinocyte cell line
nTERT and human
cervical cancer cell
line HeLa89
Overexpression / Increase in invasion
of enteric pathogen
Shigella flexneri
bacteria		 Coculture of human
keratinocyte cell line
nTERT and human
cervical cancer cell
line HeLa89
Carriers of
35delG Cx26
allele (loss of
function mutant)		 / Increase in epidermal
thickness		 Population study of
human epidermis86
Overexpression / Increase the
dissemination of
enteropathogenic
bacteria Shigella
flexneri; increase in
ATP release		 Human cervical
cancer cell line
HeLa152
Cx30 Knockout Decrease Independent of
gap junction channel
activity as GJ
structures are lacking
in normal mice		 Instrastrial fluid–
blood barrier in
cochlear of Cx30−/−
mice153
Cx32 Overexpression No
change		 Induction of TJ strands
and occludin level		 Mouse hepatocyte
cell line CHST8154
Ectopic expression Slight
increase		 Increase in levels
and/or localization
at cell borders of
occludin, claudin-1,
ZO-1 and ZO-1, which
can be reversed by
18β-glycyrrhetinic acid;
these observations are
absent in Cx26 or Cx43
transfectants		 Immortalized
Cx32-deficient
mouse hepatocytes155
Cx43 Conditional
knockout		 / Acceleration of wound
closure		 Epidermis of
Cx43Cre-ER(T)/flmice91
Knockdown with
antisense oligo
DNA		 / Acceleration of wound
closure		 Mice epidermis92
Overexpression of
Cx43K258Stop		 Defective Doubled half-life in
Cx43K258Stop, which
does not carry the
C-terminal tail, as shown
in HeLa cells		 Epidermis of
Cx43K258stop
knockin mice90
Knockdown with
siRNA		 No change Disruption of barrier
integrity only with a
concurrent knockdown
of Cx43 and desmosome
protein plakophilin-2		 Primary culture of
Sertoli cells60