Page 66 - F. Cell biology

[F. Cell biology-42]

Inhibition of TGF-β-induced Fibroblast-Myofibroblast

Transdifferentiation by JIB-04

Kyeong Min Park¹, Wan Young Kim¹, Sun Young Lee¹, Ho Shik Kim¹˙*, Seok Jun Shin²˙*

¹Department of biochemistry, The catholic university of korea, medicine of college, seoul 06591, Republic of Korea

TGF-β1 plays a critical role in fibroblast-myofibroblast transdifferentiation during development of renal fibrosis.
Recently, histone demethylase (KDM) has been reported to contribute to TGF-β1-induced expression of fibrotic
genes. In this study, we analyzed the effect of JIB-04, a chemical inhibitor of KDM4A and KDM4B, on TGF-β1-

induced transdifferentiation of NRK-49F cells, normal rat kidney interstitial fibroblast cells. Pretreatment of JIB-04

attenuated TGF-β1-induced expression of profibrotic genes such as snail, PAI-1, and α-SMA at the levels of mRNA
and protein. By confocal microscopy, JIB-04 also reduced expression of myofibroblast markers such as vimentin and
fibronectin in TGF-β1-treated cells. In addition, JIB-04 inhibited TGF-β1-induced phosphorylation of smad2 and

smad3. Collectively, these results suggest that JIB-04 may suppress TGF-β1-induced fibroblast-myofibroblast
transdifferentiation during renal fibrosis by preventing phosphorylation of smad2 and smad3.