title: Monocytes induce proximal tubular epithelial-mesenchymal transition through NF-kappa B dependent upregulation of ICAM-1.
abstract: Inflammatory cell infiltration plays a key role in the pathogenesis of tubulointerstitial damage in chronic renal diseases. In addition to secreting the profibrotic cytokines, monocytes themselves have been demonstrated to be directly associated with renal fibrogenesis. However, how infiltrating monocytes interact with resident cells and the underlying mechanisms remain elusive. In this study we investigated the effects of monocytes on phenotypic changes of human proximal tubular HK-2 cells. The typical epithelial cell morphology of HK-2 cells disappeared after co-culture with monocytes, accompanied by decreased E-cadherin expression, and increased α-SMA and fibronectin expression, suggesting that HK-2 cells undergo epithelial-mesenchymal transition (EMT). Further analysis revealed that the effects were dependent on direct contact of the two types of cells as conditioned medium had no effects. Interestingly, administration of CD18 antibody directly inhibited this process. Furthermore, by microarray and RT-PCR we found that NF-kB signaling may play a role in this process and blockade of this signaling pathway in HK-2 cells could inhibit ICAM-1 expression and EMT phenotypes. Taken together, these findings suggest that monocytes infiltration could directly induce EMT of HK-2 cells via upregulation ICAM-1 through NF-kB signaling pathway.
authors.affiliation: Institute of Nephrology, Zhong Da Hospital, Southeast University, Nanjing 210009, China.
authors.forename: Qing
authors.initials: Q
authors.lastname: Li
authors.forename: Bi-Cheng
authors.initials: BC
authors.lastname: Liu
authors.forename: Lin-Li
authors.initials: LL
authors.lastname: Lv
authors.forename: Kun-Ling
authors.initials: KL
authors.lastname: Ma
authors.forename: Xiao-Liang
authors.initials: XL
authors.lastname: Zhang
authors.forename: Aled O
authors.initials: AO
authors.lastname: Phillips
mesh_terms: D015153:Blotting, Western; D002460:Cell Line; D018920:Coculture Techniques; D017077:Culture Media, Conditioned / Q000494:pharmacology; D058750:Epithelial-Mesenchymal Transition / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics / Q000378:metabolism*; D007687:Kidney Tubules, Proximal / Q000166:cytology* / Q000378:metabolism*; D009000:Monocytes / Q000166:cytology / Q000378:metabolism* / Q000502:physiology*; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism*; D020298:U937 Cells
chemical_list: D017077:Culture Media, Conditioned; D016328:NF-kappa B; D018799:Intercellular Adhesion Molecule-1