In general these results suggested that

In general, these results suggested that EP300 and DDR1 synergistically acted as therapeutic regulators of TGF-β1 signaling in pulmonary fibrosis. Both EP300 and DDR1 Menadione mg were significantly up-regulated in IPF patients, and EP300 exerted potential fibrotic effects by activating DDR1 expression under TGF-β1 stimulation. Furthermore, pharmacological inhibition of EP300 by siRNA or inhibitors synergistically alleviated fibrotic and inflammation injury with DDR1 inhibitors in vitro and in vivo. Our results provide novel insights into the therapeutic potential of EP300 and DDR1 in the treatment of idiopathic pulmonary fibrosis or inflammatory pulmonary injury.
Competing interests
Funding source This study was supported by the National Natural Science Funds (NSFC 81573154 and 81773432), the Fundamental Research Funds of Science & Technology Department of Sichuan Province (2017JY0123), the China Postdoctoral Science Foundation (No. 2016M602696 and 2016M592679) and the open project of Chengdu University, Sichuan Industrial Institute of Antibiotics, Antibiotics Research and Re-evaluation Key Laboratory of Sichuan Province (ARRLKF17-02).
Introduction Vitiligo is an acquired, chronic depigmenting disorder of the skin characterized by gradual loss of melanocytes in depigmented areas of the skin. With a worldwide prevalence of 1%, vitiligo is considered to be the most common pigmentation disorder (Tarlé et al., 2014). Vitiligo is classified into two major forms, namely segmental and non-segmental vitiligo. The former is less common and usually occurs with a unilateral and band-shaped distribution. The latter characterized by symmetrical and bilateral white patches occurs with different clinical subtypes, including focal, acrofacial, vulgaris and universal (Ezzedine et al., 2015). Although the molecular basis is not known completely, the disappearance of melanocytes in vitiligo appears to involve with cell adhesion defects (Wagner et al., 2015). This theory has been supported by the weaker expression of two molecules identified in cell-cell adhesion, Epithelial Cadherin (E-cadherin) and Discoidin Domain Receptor Tyrosine kinase 1 (DDR1), in keratinocytes of depigmented vitiligo lesions compared to normal skin (Kim and Lee, 2010; Ricard et al., 2012). E-cadherin is an adhesive Ca2+ dependent transmembrane protein mediating tight and strong cell-cell adhesion through homophilic interactions. There is strong evidence in favour of the major role of E-cadherin in melanocytes adhesion to keratinocytes in the epidermis (Tang et al., 1994). The expression of E-cadherin in melanocytes in both non-segmental and segmental forms of vitiligo has been shown to be reduced similarly compared to normally pigmented skin emphasizing the cell adhesion defect theory as an initial step for pigment loss in vitiligo (Grill et al., 2018). DDR1 is a transmembrane tyrosine kinase receptor that forms a complex with E-cadherin at cell junctions and plays a physiological role through stabilization of E-cadherin and E-cadherin-mediated cell aggregation (Eswaramoorthy et al., 2010). The results of previous studies showed a significant reduction in DDR1 expression level in lesional compared to non-lesional vitiligo skin which adds to the cumulative evidence pointing to DDR1 as a major factor causing impaired adhesion process involved in vitiligo (Elgarhy et al., 2016; Reichert-Faria et al., 2013).