n is down regulated in the psoriatic lesions compared to normal or uninvolved psoriatic skin. We now show that miR-197 leads to decreased proliferation and migration of KC in vitro, along with increased expression of KC differentiation marker, involucrin and keratin 10. It is noteworthy that despite the observed inhibition of proliferation of HaCaT cells stably over expressing miR-197, exposure of HaCaT cells to antago-miR-197 did not affect cell proliferation. The experiment shown in figure S3 and discussed in the results, proves that the antago-miR-197 is indeed active, since it releases miR-197 effect on reporter mRNA containing the 39UTR of IL22RA1. The lack of antago-miR effect on proliferation suggests that in order to inhibit proliferation it is sufficient to over express, in large excess, one miRNA. However, in order to unbalance this very complex, multifactorial system and induce hyper proliferation phenotype, it is possible that the partial of only one of these components is not sufficient. In this study, we establish that the IL-22 receptor subunit IL22RA1 is a target of miR-197. Interestingly, treatment of cells with IL-22 increases the expression of miR-197. Bioinformatics predict that miR-197 targets the two units of the hetrodimeric IL-22 receptor, namely IL22RA1 and IL-10RB. Our work shows that only IL22RA1, but not IL10RB, is a bona-fide target of miR-197. IL22RA1 subunit is part of the receptor of both IL-22 and IL-20. Both cytokines are up regulated in psoriasis and have similar biological effects. While IL-22 utilizes only the IL22RA1/IL-10RB receptor, IL-20 can utilize also the IL-20RA1/IL-20RA2 receptor. PubMed ID:http://www.ncbi.nlm.nih.gov/pubmed/1967325 However, in psoriasis, only the IL22RA1 subunit is up regulated. This implies that miR-197, by controlling IL22RA1, can fine-tune several aspects of cytokine signaling pathways. Moreover, the fact that miR-197 targets only the IL22RA1 subunit of the IL-22 receptor emphasizes the role it might play in the pathogenesis of psoriasis. There is no mouse homolog of miR-197. The miRviewer program reveals that the miR-197 gene exists only in some placental mammals. According to the miRBase data, miR-197 gene is even more infrequent, being present only in primates, horse, cow and Crosstalk Sutezolid web between IL-22 Signaling and miR-197 dog. IL-22 receptor gene is expressed in non-mammals as well as in mammals. Yet the binding site of miR-197 in the 39UTR of IL22RA1 is found only in primates, dog, cow and horse but not in Crosstalk between IL-22 Signaling and miR-197 normal healthy humans. They observed a significant increase in global DNA methylation level in psoriatic peripheral blood mononuclear cells relative to normal controls. Furthermore, using immunohistochemistry they found extensive DNA methylation staining in skin lesion biopsies from psoriatic patients compared to normal controls. Moreover, they found a significant positive correlation between methylation staining in the skin and Psoriasis Area and Severity Index scores among psoriatic patients. The same group showed that global histone PubMed ID:http://www.ncbi.nlm.nih.gov/pubmed/19674970 H4 hypoacetylation was observed in PBMCs from psoriasis vulgaris patients. In the present study we did not detect any difference in cytosine methylation of the putative miR-197 promoter from biopsies of normal, uninvolved, or psoriatic skins. These results are consistent with the results of Zhang P. et al.. The fact that there is no change in the methylation of this region between psoriatic and normal skin could be either due to lack of corr

First, the expression of IMP3 in RCC cell lines and HKC cells were examined

About author

Leave a reply

You must be logged in to post a comment.