Ectopic expression of Ligand-of-Numb protein X promoted TGF-beta induced epithelial to mesenchymal transition of proximal tubular epithelial cells.
Ligand-of-Numb protein X (LNX) was initially characterized as a RING finger type E3 ubiquitin ligase that targeted the intrinsic cell fate determinant Numb for ubiquitination dependent degradation. However, the physiological function of LNX remains largely unknown. In the present study, we demonstrate that ectopic expression of LNX in human proximal tubular epithelial cells (HK-2 cells) significantly enhanced TGF-beta1 induced epithelial to mesenchymal transition (EMT). The EMT-promoting effect of LNX manifested as strong inhibition of E-cadherin expression, enhanced expression of vimentin, fibronectin or PAI-1, and increased cell migration. This function of LNX was shown to be independent of its ligase activity because ectopic expression of a mutant form of LNX (C48ALNX) that lacks E3 ligase activity had the similar effect as the wild-type LNX. Overexpression of E-cadherin could inhibit LNX augmented EMT. This study suggests a potential role for LNX in promoting EMT in human proximal tubular epithelial cells.
Nie
Jing
J
Department of Nephrology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou 510080, PR China.
Wu
Qiaoyuan
Q
Liu
Wei
W
Zhu
Fengxin
F
Qiu
Fanghua
F
Zhou
Qin
Q
Fan
Jinjin
J
Dong
Xiuqing
X
Yu
Xueqing
X
D015820:Cadherins / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects*; D002460:Cell Line; D002465:Cell Movement / Q000187:drug effects; D004847:Epithelial Cells / Q000166:cytology* / Q000187:drug effects / Q000201:enzymology*; D005109:Extracellular Matrix / Q000378:metabolism; D005786:Gene Expression Regulation; D006801:Humans; D007687:Kidney Tubules, Proximal / Q000166:cytology* / Q000187:drug effects / Q000201:enzymology*; D008024:Ligands; D016212:Transforming Growth Factor beta / Q000494:pharmacology*; D044767:Ubiquitin-Protein Ligases / Q000378:metabolism*; D014746:Vimentin / Q000096:biosynthesis
D015820:Cadherins; D008024:Ligands; D016212:Transforming Growth Factor beta; D014746:Vimentin; D044767:Ubiquitin-Protein Ligases