Claudin-7 indirectly regulates the integrin/FAK signaling pathway in human colon cancer tissue.

The claudin family of proteins is integral to the structure and function of tight junctions. The role of claudin-7 (Cldn-7, CLDN7) in regulating the integrin/focal adhesion kinase (FAK)/ERK signaling pathway remains poorly understood. Therefore, we investigated differences in gene expression, primarily focusing on CLDN7 and integrin/FAK/ERK signaling pathway genes, between colon cancer and adjacent normal tissues. Quantitative real-time reverse transcription-PCR and immunohistochemistry were utilized to verify the results of mRNA and protein expression, respectively. In silico analysis was used to predict co-regulation between Cldn-7 and integrin/FAK/ERK signaling pathway components, and the STRING database was used to analyze protein-protein interaction pairs among these proteins. Meta-analysis of expression microarrays in The Cancer Genome Atlas (TCGA) database was used to identify significant correlations between Cldn-7 and components of predicted genes in the integrin/FAK/ERK signaling pathway. Our results showed marked cancer stage-specific decreases in the protein expression of Cldn-7, Gelsolin, MAPK1 and MAPK3 in colon cancer samples, and the observed changes for all proteins except Cldn-7 were in agreement with changes in the corresponding mRNA levels. Cldn-7 might indirectly regulate MAPK3 via KRT8 due to KRT8 co-expression with MAPK3 or CLDN7. Our bioinformatics methods supported the hypothesis that Cldn-7 does not directly regulate any genes in the integrin/FAK/ERK signaling pathway. These factors may participate in a common network that regulates cancer progression in which the MAPK pathway serves as the central node.

cPKCγ alleviates ischemic injury through modulating synapsin Ia/b phosphorylation in neurons of mice.

Conventional protein kinase C (cPKC)γ and synapsin Ia/b have been implicated in the development of ischemic stroke, but their relationships and functions are unclear. In the present study, the oxygen-glucose deprivation (OGD)-induced ischemic insult in primary cultured cortical neurons in vitro and middle cerebral artery occlusion (MCAO)-induced ischemic stroke model in vivo were used to elucidate the function of cPKCγ and its modulation on synapsin Ia/b phosphorylation in ischemic stroke. We found that cPKCγ knockout significantly increased the infarct volume of mice after 1 h MCAO/72 h reperfusion by using triphenyltetrazolium chloride (TTC) staining. In the primarily cultured cortical neurons, cPKCγ knockout also aggravated the OGD-induced cell death and morphological damage of neurites, while cPKCγ restoration could alleviate the ischemic injury. Among the five phosphorylation sites of synapsin Ia/b, only the phosphorylation levels of Ser549 and 553 could be modulated by cPKCγ in neurons following 0.5 h OGD/24 h reoxygenation. In addition, we found that cPKCγ and synapsin Ia/b could be reciprocally co-immunoprecipitated in the cerebral cortex of MCAO mice. Taken together, we proposed that cPKCγ alleviates ischemic injury through modulating Ser549/553- synapsin Ia/b phosphorylation in neurons of mice.