Human gingival fibroblasts (HGFs) in the oral cavity are constantly exposed to bacteria and may or may not trigger immune responses. Lately, critical bacterial signaling molecules, cyclic-di-adenosine monophosphate (c-di-AMP) and cyclic-di-guanosine monophosphate (c-di-GMP) which play important roles in immune response to pathogens were discovered. However, response of HGFs to these essential bacterial second messengers has not been fully characterized. As a step towards understanding the response of HGFs to these molecules, we carried out a global proteomics analysis of HGFs treated with either c-di-AMP or c-di-GMP. We found differential expression of several proteins in cyclic dinucleotide (CDN) treated HGFs. Analysis of the differentially expressed proteins showed that interferon signaling proteins such as Interferon-induced GTP-binding protein Mx1 (MX-1), Interferon-induced protein with tetratricopeptide repeats 1 (IFIT-1) and Interferon-induced protein with tetratricopeptide repeats 3 (IFIT-3) were the most significantly upregulated proteins. Functional network analysis showed that 21 biological pathways were significantly regulated by both CDNs while others were differentially regulated. Additionally, the functional analysis also predicted increased proliferation of fibroblast cell lines by c-di-GMP. These findings highlight the critical role played by HGFs in the presence of invading pathogens in the oral mucosa by their activation or inhibition of various molecular pathways.
[doi:10.25345/C5SZ3F]
[dataset license: CC0 1.0 Universal (CC0 1.0)]
Keywords: c-di-GMP, c-di-AMP, proteomics, fibroblast, mass spectrometry
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Dr. Herman O. Sintim, Purdue University, USA |
Submitting User: | uma_aryal |
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