JOURNAL ARTICLE

FHL2 promotes tubular epithelial-to-mesenchymal transition through modulating β-catenin signalling

Ting Cai, Danqin Sun, Ying Duan, Yumei Qiu, Chunsun Dai, Junwei Yang, Weichun He
Journal of Cellular and Molecular Medicine 2018, 22 (3): 1684-1695
29193729
β-Catenin signalling plays an important role in regulating tubular epithelial-to-mesenchymal transition (EMT), an indispensable programme for driving renal fibrosis. As an adapter protein, four and a half LIM domain protein 2 (FHL2) acts as a coregulator of β-catenin in several other cell types. To determine whether FHL2 affects β-catenin signalling and thus is involved in tubular EMT, we examined its expression and function in the process of TGF-β1-induced EMT. FHL2 mRNA and protein were induced by TGF-β1 in rat tubular epithelial cells (NRK-52E), an effect that intracellular Smad signalling was required. Ectopic expression of FHL2 inhibited E-cadherin and enhanced α-smooth muscle actin (α-SMA) and fibronectin expression, whereas knockdown of FHL2 partially restored E-cadherin and reduced α-SMA and fibronectin induction stimulated by TGF-β1. Overexpression of FHL2 increased β-catenin dephosphorylation (Ser37/Thr41), nuclear translocation and β-catenin-mediated transcription and up-regulated expression of β-catenin target, EMT-related genes, such as Snail, Twist, vimentin, plasminogen activator inhibitor-1 and matrix metalloproteinase-7. Conversely, knockdown of FHL2 increased β-catenin phosphorylation (Ser33/37/Thr41), decreased its nuclear translocation and inhibited β-catenin-mediated transcription and target genes expression. TGF-β1 induced a FHL2/β-catenin interaction in NRK-52E cells, especially in the nuclei. In a mouse model of obstructive nephropathy, FHL2 mRNA and protein were induced in a time-dependent fashion, and the extent and pattern of renal β-catenin activation were positively correlated with FHL2 induction. Collectively, this study suggests that FHL2, via modulating β-catenin signalling, may implicate in regulation of TGF-β1-mediated tubular EMT and could be a potential therapeutic target for fibrotic kidney disease.

Full Text Links

Find Full Text Links for this Article

Discussion

You are not logged in. Sign Up or Log In to join the discussion.

Trending Papers

Remove bar
Read by QxMD icon Read
29193729
×

Save your favorite articles in one place with a free QxMD account.

×

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"