Emerging Transcriptional Mechanisms in the Regulation of Epithelial to Mesenchymal Transition and Cellular Plasticity in the Kidney

Journal of Clinical Medicine

Letizia De Chiara¹  John Crean²  David A. Brenner²  Tatiana Kisseleva² 

[1] Diabetes Complications Research Centre, UCD School of Biomolecular and Biomedical Science, University College Dublin, Belfield, Dublin 4, Ireland

关键词: EMT;    Kidney;    SNAI1;    TGFβ signaling;    plasticity;    PRC2;    SMAD3;   

DOI  :  10.3390/jcm5010006

来源: mdpi

【 摘 要 】

Notwithstanding controversies over the role of epithelial to mesenchymal transition in the pathogenesis of renal disease, the last decade has witnessed a revolution in our understanding of the regulation of renal cell plasticity. Significant parallels undoubtedly exist between ontogenic processes and the initiation and propagation of damage in the diseased kidney as evidenced by the reactivation of developmental programmes of gene expression, in particular with respect to TGFβ superfamily signaling. Indeed, multiple signaling pathways converge on a complex transcriptional regulatory nexus that additionally involves epigenetic activator and repressor mechanisms and microRNA regulatory networks that control renal cell plasticity. It is becoming increasingly apparent that differentiated cells can acquire an undifferentiated state akin to “stemness” which is leading us towards new models of complex cell behaviors and interactions. Here we discuss the latest findings that delineate new and novel interactions between this transcriptional regulatory network and highlight a hitherto poorly recognized role for the Polycomb Repressive Complex (PRC2) in the regulation of renal cell plasticity. A comprehensive understanding of how external stimuli interact with the epigenetic control of gene expression, in normal and diseased contexts, establishes a new therapeutic paradigm to promote the resolution of renal injury and regression of fibrosis.

【 授权许可】

CC BY   
© 2016 by the authors; licensee MDPI, Basel, Switzerland.