Knockdown of survivin results in inhibition of epithelial to mesenchymal transition in retinal pigment epithelial cells by attenuating the TGFβ pathway

Peng Zhang, Guannan Zhao, Liang Ji, Jinggang Yin, Lu Lu, Wei Li, Guomin Zhou, Edward Chaum, Junming Yue

Research output: Contribution to journalArticle

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Abstract

Proliferative vitreoretinopathy (PVR) is a common complication of open globe injury and the most common cause of failed retinal detachment surgery. The response by retinal pigment epithelial (RPE) cells liberated into the vitreous includes proliferation and migration; most importantly, epithelial to mesenchymal transition (EMT) of RPE plays a central role in the development and progress of PVR. For the first time, we show that knockdown of BIRC5, a member of the inhibitor of apoptosis protein family, using either lentiviral vector based CRISPR/Cas9 nickase gene editing or inhibition of survivin using the small-molecule inhibitor YM155, results in the suppression of EMT in RPE cells. Knockdown of survivin or inhibition of survivin significantly reduced TGFβ-induced cell proliferation and migration. We further demonstrated that knockdown or inhibition of survivin attenuated the TGFβ signaling by showing reduced phospho-SMAD2 in BIRC5 knockdown or YM155-treated cells compared to controls. Inhibition of the TGFβ pathway using TGFβ receptor inhibitor also suppressed survivin expression in RPE cells. Our studies demonstrate that survivin contributes to EMT by cross-talking with the TGFβ pathway in RPE cells. Targeting survivin using small-molecule inhibitors may provide a novel approach to treat PVR disease.

Original languageEnglish (US)
Pages (from-to)573-578
Number of pages6
JournalBiochemical and Biophysical Research Communications
Volume498
Issue number3
DOIs
StatePublished - Apr 6 2018

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Retinal Pigments
Epithelial-Mesenchymal Transition
Proliferative Vitreoretinopathy
Epithelial Cells
Clustered Regularly Interspaced Short Palindromic Repeats
Inhibitor of Apoptosis Proteins
Molecules
Deoxyribonuclease I
Cell proliferation
Retinal Detachment
Surgery
Cell Movement
Genes
Cells
Cell Proliferation
Wounds and Injuries

All Science Journal Classification (ASJC) codes

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Knockdown of survivin results in inhibition of epithelial to mesenchymal transition in retinal pigment epithelial cells by attenuating the TGFβ pathway. / Zhang, Peng; Zhao, Guannan; Ji, Liang; Yin, Jinggang; Lu, Lu; Li, Wei; Zhou, Guomin; Chaum, Edward; Yue, Junming.

In: Biochemical and Biophysical Research Communications, Vol. 498, No. 3, 06.04.2018, p. 573-578.

Research output: Contribution to journalArticle

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