@Article{ecn.2016.0373,
AUTHOR = {Li Liu, Fu-gang Li, Man Yang, Li Wang, Yue Chen, Li Wang, Wen Ji, Jun-ming Fan},
TITLE = {Effect of pro-inflammatory interleukin-17A on epithelial cell phenotype inversion in HK-2 cells <i>in vitro</i>},
JOURNAL = {European Cytokine Network},
VOLUME = {27},
YEAR = {2016},
NUMBER = {2},
PAGES = {34--40},
URL = {http://www.techscience.com/ECN/v27n2/65539},
ISSN = {1952-4005},
ABSTRACT = {Background: Renal interstitial fibrosis (RIF) is a pathological change common to a variety of chronic
renal diseases, ultimately progressing to end-stage renal failure. It is believed that epithelial cell phenotype inversion
plays an important role in RIF, which is characterized by expression of the mesenchymal maker α-SMA, loss of
the epithelial maker E-cadherin, and enhanced secretion of extracellular matrix. IL-17, a newly discovered proinflammatory
cytokine, has recently been reported to play an important role in tissue fibrosis, involving pulmonary,
liver, intestine and skin tissues. This study aimed to investigate whether IL-17A, a member of the IL-17 family, can
induce epithelial cell phenotype inversion, and to explore the molecular mechanism of this phenotype inversion, in
vitro. Methods: HK-2 cells were cultured and incubated with IL-17A. Cell proliferation was measured by CCK-8
assay, and the secretion of types I and III collagen was detected by ELISA in dose-dependent and time-dependent
experiments. To find out whether IL-17A can induce epithelial cell phenotype inversion, HK-2 cells were stimulated
with 80 ng/mL of IL-17A and 10 ng/mL of TGF-β1 as a positive control, for 72 h. To explore the potential signaling
pathway, anti-TGF-β1 antibody was added before IL-17A treatment. At the same time, anti-TGF-β1 antibody alone
was added to the medium as the negative control group. The expression of types I and III collagen, α-SMA and
E-cadherin proteins, and mRNA was measured by real-time PCR, western blotting and immuno-histochemistry.
Results: IL-17A promoted the proliferation of HK-2 cells and secretion of types I and III collagen in a dose-dependent
and time-dependent manner. Compared with the normal control, IL-17A could stimulate the expression of α-SMA,
types I and III collagen, and suppressed the expression of E-cadherin in HK-2 cells. Incubation of IL-17A with
TGF-β1 antibody decreased significantly the expression of α-SMA, but increased the expression of E-cadherin in
HK-2 cells. Conclusion: Our results suggest that IL-17A might promote the proliferation of HK-2 cells and secretion
of extracellular matrix, and induce epithelial cell phenotype inversion via a TGF-β1-dependent pathway. Blocking
the pro-inflammatory cytokine IL-17A might be a potential target for the treatment of fibrotic kidney disease.},
DOI = {10.1684/ecn.2016.0373}
}