Role of the JNK signaling PathWay in downregulation of connexin43 by TNF-α in human corneal fibroblasts

Kazuhiro Kimura, Tomoko Orita, Naoyuki Morishige, Teruo Nishida, Koh Hei Sonoda

Research output: Contribution to journalArticlepeer-review

19 Citations (Scopus)


Purpose/Aim: Proinflammatory cytokines such as tumor necrosis factor (TNF)-α contribute to corneal inflammation. Corneal stromal fibroblasts are connected to each other via gap junctions. We have now examined the role of mitogen-activated protein kinase (MAPK) signaling pathways in TNF-α-induced downregulation of the gap junction protein connexin43 (Cx43) in human corneal fibroblasts. Materials and Methods: Cultured human corneal fibroblasts were exposed to TNF-α in the absence or presence of inhibitors of MAPK signaling pathways. Expression of Cx43 was evaluated by immunofluorescence and immunoblot analyses. Gap-junctional intercellular communication (GJIC) was measured with a dye-coupling assay. Results: TNF-α reduced the abundance of Cx43 in human corneal fibroblasts (as revealed by immunoblot analysis) as well as induced the loss of specific staining for this protein (as revealed by immunofluorescence analysis). These effects of TNF-α were attenuated by an inhibitor of c-Jun NH2-terminal kinase (JNK inhibitor II) but not by inhibitors of signaling by extracellular signal-regulated kinase (PD98059) or by p38 MAPK (SB203580). JNK inhibitor II also attenuated the inhibitory effect of TNF-α on GJIC. Conclusions: The inhibitory effects of TNF-α on Cx43 expression and GJIC in human corneal fibroblasts are mediated, at least in part, by the JNK signaling pathway, which therefore likely plays a role in corneal inflammation.

Original languageEnglish
Pages (from-to)926-932
Number of pages7
JournalCurrent Eye Research
Issue number9
Publication statusPublished - Sept 2013
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Ophthalmology
  • Sensory Systems
  • Cellular and Molecular Neuroscience


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