HMGA2 Modulates the TGF β/Smad, TGFβ/ERK and Notch Signaling Pathways in human Lens Epithelial-Mesenchymal Transition.

HMGA2 Modulates the TGFβ/Smad, TGFβ/ERK and Notch Signaling Pathways in human Lens Epithelial-Mesenchymal Transition. Curr Mol Med. 2018 Jul 04;: Authors: Hou M, Bao X, Luo F, Chen X, Liu L, Wu M Abstract Multiple signaling pathways contribute to lens fibrosis, where transforming growth factor beta (TGFβ)-mediated signaling plays a central role. Canonical TGFβ/Smad signaling predominates, and noncanonical TGFβ/extracellular signal-regulated kinase (ERK) signaling and Notch signaling contribute to TGFβ-triggered epithelial-mesenchymal transition (EMT) in lens epithelial cells (LECs). These three signaling pathways coordinately promote EMT. The mechanism of crosstalk among these pathways remains obscure. High mobility group protein A2 (HMGA2) is an architectural transcription factor required for TGFβ to elicit EMT in mammary epithelial cells, and HMGA2 plays an important role in organ development and in the progression of many malignant neoplasms. However, the regulatory effect of HMGA2 on lens fibrosis has not yet been delineated. Herein, the present study demonstrated that HMGA2 was upregulated both in human anterior subcapsular cataracts (ASCs) and TGFβ2 induced EMT in human LECs, while individual blockade of TGFβ/Smad, TGFβ/ERK or Notch signaling by a specific pharmacological inhibitor (SB431542, U0126 or DAPT, respectively) markedly abrogated the upregulation of HMGA2 expression. Downregulation of HMGA2 expression by sma...
Source: Current Molecular Medicine - Category: Molecular Biology Authors: Tags: Curr Mol Med Source Type: research