## Abstract ## Objective Mitogen‐activated protein kinases (MAPKs) are activated by proinflammatory stimuli. MAPK phosphatases (MKPs), in particular MKP‐1, have been identified as endogenous negative regulators of MAPK activation. Since MAPKs are known to be important in rheumatoid arthritis (RA)
Up-regulation of the tight-junction protein ZO-1 by substance P and IGF-1 in A431 cells
✍ Scribed by Ji-Ae Ko; Shizuka Murata; Teruo Nishida
- Publisher
- John Wiley and Sons
- Year
- 2009
- Tongue
- English
- Weight
- 276 KB
- Volume
- 27
- Category
- Article
- ISSN
- 0263-6484
- DOI
- 10.1002/cbf.1587
No coin nor oath required. For personal study only.
✦ Synopsis
Abstract
The formation of a barrier by tight junctions is important in epithelia of various tissues. Substance P (SP) and insulin‐like growth factor (IGF)–1 synergistically promote barrier function in the corneal epithelium. We have now examined the effects of SP and IGF‐1 on expression of the tight‐junction protein zonula occludens (ZO)–1 in A431 human epidermoid carcinoma cells. Reverse transcription–polymerase chain reaction (RT–PCR) and immunoblot analyses revealed that SP and IGF‐1 increased the amounts of ZO‐1 mRNA and protein in these cells in a concentration‐dependent manner, with neither SP nor IGF‐1 alone having such an effect. The SP‐ and IGF‐1–induced up‐regulation of ZO‐1 was accompanied by phosphorylation of extracellular signal–regulated kinase (ERK), and both of these effects were blocked by PD98059, an inhibitor of ERK activation. SP and IGF‐1 also increased the transepithelial electrical resistance (TER) (an indicator of barrier function) of an A431 cell monolayer in a manner sensitive to PD98059. Our results thus suggest that the synergistic induction of ZO‐1 expression by SP and IGF‐1 may promote barrier function in skin epithelial cells. Copyright © 2009 John Wiley & Sons, Ltd.
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