p38 MAP-kinase regulates function of gap and tight junctions during regeneration of rat hepatocytes

Yamamoto, Takumi; Kojima, Takashi; Murata, Masaki; Takano, Kenichi; Go, Mitsuru; Hatakeyama, Naoko; Chiba, Hideki; Sawada, Norimasa

doi:10.1016/j.jhep.2004.12.033

Cited by 48 publications

(33 citation statements)

References 48 publications

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“…p38 inhibitor, SB203580 (SB) can protect the mouse from partial hepatectomy, the mechanism is likely to be that SB inhibited the down-regulation of Cx32 resulting in the maintenance of the structure of gap junctions35. Given the correlation between Cx32 expression and hepatocyte functional maintenance, we hypothesized that enhanced hepatocyte maturity might be achieved by modulating Cx32 directly or indirectly in the process of hESCs’ hepatic differentiation by those regulators we mentioned above.…”

mentioning

confidence: 99%

Connexin 32-mediated cell-cell communication is essential for hepatic differentiation from human embryonic stem cells

Qin¹,

Chang²,

Wang³

et al. 2016

Sci Rep

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Gap junction-mediated cell-cell interactions are highly conserved and play essential roles in cell survival, proliferation, differentiation and patterning. We report that Connexin 32 (Cx32)-mediated gap junctional intercellular communication (GJIC) is necessary for human embryonic stem cell-derived hepatocytes (hESC-Heps) during step-wise hepatic lineage restriction and maturation. Vitamin K2, previously shown to promote Cx32 expression in mature hepatocytes, up-regulated Cx32 expression and GJIC activation during hepatic differentiation and maturation, resulting in significant increases of hepatic markers expression and hepatocyte functions. In contrast, negative Cx32 regulator 2-aminoethoxydiphenyl borate blocked hESC-to-hepatocyte maturation and muted hepatocyte functions through disruption of GJIC activities. Dynamic gap junction organization and internalization are phosphorylation-dependent and the p38 mitogen-activated protein kinases pathway (MAPK) can negatively regulate Cxs through phosphorylation-dependent degradation of Cxs. We found that p38 MAPK inhibitor SB203580 improved maturation of hESC-Heps correlating with up-regulation of Cx32; by contrast, the p38 MAPK activator, anisomycin, blocked hESC-Heps maturation correlating with down-regulation of Cx32. These results suggested that Cx32 is essential for cell-cell interactions that facilitate driving hESCs through hepatic-lineage maturation. Regulators of both Cx32 and other members of its pathways maybe used as a promising approach on regulating hepatic lineage restriction of pluripotent stem cells and optimizing their functional maturation.

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confidence: 99%

Connexin 32-mediated cell-cell communication is essential for hepatic differentiation from human embryonic stem cells

Qin¹,

Chang²,

Wang³

et al. 2016

Sci Rep

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“…Another study using Escherichia coli showed that ERK1/2 was activated in T84 cells, but did not induce TJ barrier disruptions as measured by TEER [41]. Recent studies suggest that TJs are regulated in some tissues in vitro and in vivo through the p38 MAP kinase signaling pathway [24,42,43]. TGF(transforming growth factor)-b3 regulates the blood-testis barrier in vivo and in vitro via the p38 MAP kinase pathway [42].…”

Section: Discussionmentioning

confidence: 99%

“…TGF(transforming growth factor)-b3 regulates the blood-testis barrier in vivo and in vitro via the p38 MAP kinase pathway [42]. Yamamoto et al reported that expression and function of TJs during regeneration of rat hepatocytes are partly controlled via the p38 MAP kinase signaling pathway [43]. Thus, the roles of MAP kinases in epithelial barrier function and TJs are numerous and may depend on cell type or stimulant specificity.…”

Section: Discussionmentioning

confidence: 99%

Wip1 protects hydrogen peroxide-induced colonic epithelial barrier dysfunction

Oshima

Sasaki

Kataoka

et al. 2007

Cell. Mol. Life Sci.

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Tight junctions (TJs) create a paracellular permeability barrier. Although reactive oxygen species have been implicated as mediators of inflammation in inflammatory bowel diseases, their influence on the function of colonic epithelial TJs remains unknown. Oxidative stress-mediated colonic epithelial permeability was significantly attenuated by a p38 mitogen-activated protein (MAP) kinase inhibitor, SB203580. Although the amount of TJ proteins was not altered, hydrogen peroxide (H2O2) changed the localization of claudin-4 protein from an NP-40 insoluble fraction to a soluble fraction and from an apical TJ to lateral membrane. The p38 MAP kinase inactivator Wip1 significantly attenuated phosphorylation of p38 MAP kinase, and oxidative stress mediated permeability. H2O2-induced changes in claudin-4 localization were abolished by SB203580 pretreatment as well as Wip1-expressing adenovirus infection. This is the first study to demonstrate that exogenous Wip1 functions to protect oxidative stress-mediated colonic mucosal permeability and that H2O2-induced claudin-4 dislocalization is abolished by Wip1.

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“…In the rat liver, claudin-2 shows a lobular gradient increasing from periportal to pericentral hepatocytes, whereas claudin-1 and -3 are expressed in the whole liver lobule (Rahner et al 2001;Yamamoto et al 2005). Although it is thought that claudin-2 may be a key molecule in hepatic tight junctions (Imamura et al 2007; Kojima et al 2008;Yamamoto et al 2005), the physiological functions and regulation of claudin-2 in hepatocytes remain unclear. To elucidate these questions we used WIF-B9 cells that present the advantage of being well polarized and expressing a robust level of claudin-2, without expression of claudin-1, -3 and -5 (present study and B. Grosse and D. Cassio, unpublished results).…”

Section: Introductionmentioning

confidence: 99%

Knockdown of tight junction protein claudin-2 prevents bile canalicular formation in WIF-B9 cells

Son

Kojima

Decaëns

et al. 2008

Histochem Cell Biol

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The polarization of hepatocytes involves formation of functionally distinct sinusoidal (basolateral) and bile canalicular (apical) plasma membrane domains that are separated by tight junctions. Although various molecular mechanisms and signaling cascades including polarity complex proteins may contribute to bile canalicular formation in hepatocytes, the role of tight junction proteins in bile canalicular formation remains unclear. To investigate the role of the integral tight junction protein claudin-2 in bile canalicular formation, we depleted claudin-2 expression by siRNA in the polarized hepatic cell line WIF-B9 after treatment with or without phenobarbital. When WIF-B9 cells were treated with phenobarbital, claudin-2 expression and tight junction strands were markedly increased together with induction of canalicular formation with a biliary secretion function. Knockdown of claudin-2 prevented bile canalicular formation after treatment with or without phenobarbital. Furthermore, knockdown of claudin-2 caused a change from a hepatic polarized phenotype to a simple polarized phenotype, together with upregulation of pLKB1, pMAPK, pAkt and pp38 MAPK, but not pMLC, PTEN or cdc42, and an increase of intracellular vacuoles, which were present before bile canalicular formation. These results suggest that claudin-2 may affect not only the bile canalicular seal but also bile canalicular formation.

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p38 MAP-kinase regulates function of gap and tight junctions during regeneration of rat hepatocytes

Cited by 48 publications

References 48 publications

Connexin 32-mediated cell-cell communication is essential for hepatic differentiation from human embryonic stem cells

Connexin 32-mediated cell-cell communication is essential for hepatic differentiation from human embryonic stem cells

Wip1 protects hydrogen peroxide-induced colonic epithelial barrier dysfunction

Knockdown of tight junction protein claudin-2 prevents bile canalicular formation in WIF-B9 cells

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