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Oral submucous fibrosis (OSF) has been recognized as a potentially malignant disorder and is characterized by inflammation and the deposition of collagen. Among various regulators of fibrogenesis, microRNAs (miR) have received great attention but the detailed mechanisms underlying the miR-mediated modulations remain largely unknown. Here, we showed that miR-424 was aberrantly overexpressed in OSF tissues, and then we assessed its functional role in the maintenance of myofibroblast characteristics. Our results demonstrated that the suppression of miR-424 markedly reduced various myofibroblast activities (such as collagen contractility and migration ability) and downregulated the expression of fibrosis markers. Moreover, we showed that miR-424 exerted this pro-fibrosis property via direct binding to TGIF2, an endogenous repressor of the TGF-β signaling. In addition, our findings indicated that overexpression of miR-424 activated the TGF-β/Smad pathway, leading to enhanced myofibroblast activities. Altogether, our data revealed how miR-424 contributed to myofibroblast transdifferentiation, and targeting the miR-424/TGIF2 axis may be a viable direction for achieving satisfactory results from OSF treatment.

Background: Di(2-ethylhexyl)phthalate (DEHP) is one of the phthalates most widely used to manufacture various plastic products. However, the potential effects of DEHP on erythropoiesis have not been investigated comprehensively. Here, we aimed to investigate whether DEHP modulate the function of haematopoietic stem and progenitor cells (HSPCs) to influence erythropoiesis, and to explore the associated mechanisms.Results: In the present study, human cell lines with a capacity to differentiate into erythroid cells and murine bone marrow cells were treated with DEHP. DEHP not only impaired HSPC function but also suppressed erythroid differentiation in a dose-dependent manner. In addition, DEHP removal restored HSPC activity. To explore how DEHP interferes with erythroid differentiation, we focused on energy metabolism and Klotho expression. DEHP suppressed erythroid differentiation via upregulation of Klotho expression in erythroblasts and not via cellular bioenergetic modulation.Conclusions: Here, we have demonstrated a novel pathophysiological role of DEHP in erythroid differentiation. DEHP impaired erythroid differentiation by inducing Klotho expression and not by reprogramming cellular bioenergetic profiles during differentiation.