Dexamethasone prevents monocyte-induced tubular epithelial-mesenchymal transition in HK-2 cells.
Epithelial-mesenchymal transition (EMT) is a key cellular event in the early stage of tubulointerstitial fibrosis (TIF). Monocyte infiltration plays an important role in the progression of TIF. We have previously demonstrated that monocytes can directly induce HK-2 cell transition by direct contact. Dexamethasone, an important anti-inflammatory and immunosuppressant agent, has been widely used in renal disease for decades. Whether it could influence the monocyte and HK-2 cell interaction and prevent EMT is still uncertain. In this study, we found that the typical epithelial cell morphology of HK-2 cells disappeared 24 h after co-culture with monocytes, and dexamethasone significantly prevented this change in a dose-dependent manner. In addition, we found that dexamethasone prevented monocytes from binding to HK-2 cells by inhibiting ICAM-1 expression on HK-2 cells. Further analysis demonstrated that there was increased E-cadherin expression and decreased α-SMA and fibronectin expression after co-culture with dexamethasone, suggesting that dexamethasone prevents monocyte-induced HK-2 cell transition. The nuclear transcription factor κB (NF-κB) pathway played an important role in this process. These findings suggest a novel mechanism by which corticosteroids may delay the progression of TIF via preventing EMT.
Institute of Nephrology, Zhong Da Hospital, Southeast University, Nanjing, China.
Qing
Q
Li
Lin-Li
LL
Lv
Min
M
Wu
Xiao-Liang
XL
Zhang
Hong
H
Liu
Bi-Cheng
BC
Liu
D000199:Actins / Q000096:biosynthesis; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D015820:Cadherins / Q000096:biosynthesis; D002448:Cell Adhesion; D002454:Cell Differentiation / Q000187:drug effects; D002460:Cell Line; D018920:Coculture Techniques; D003907:Dexamethasone / Q000494:pharmacology*; D004847:Epithelial Cells / Q000502:physiology; D058750:Epithelial-Mesenchymal Transition / Q000187:drug effects*; D005353:Fibronectins / Q000096:biosynthesis; D006801:Humans; D007249:Inflammation; D018799:Intercellular Adhesion Molecule-1 / Q000096:biosynthesis / Q000378:metabolism; D007668:Kidney / Q000378:metabolism / Q000473:pathology; D007674:Kidney Diseases / Q000188:drug therapy / Q000517:prevention & control; D009000:Monocytes / Q000166:cytology / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism*; D009395:Nephritis, Interstitial / Q000188:drug therapy* / Q000517:prevention & control
C541116:ACTA2 protein, human; D000199:Actins; D000893:Anti-Inflammatory Agents; D015820:Cadherins; D005353:Fibronectins; D016328:NF-kappa B; D018799:Intercellular Adhesion Molecule-1; D003907:Dexamethasone