CCAAT/Enhancer-binding protein delta contributes to myofibroblast transdifferentiation and renal disease progression

Journal of the American Society of Nephrology : JASN
Masanobu TakejiTakeshi Miwa

Abstract

Myofibroblasts are pivotal participants in pathologic processes in a wide variety of organs, such as lung, liver, and kidney, by producing several inflammatory cytokines and extracellular matrices. The mechanism by which transdifferentiation from original cell to myofibroblast occurs, however, is still unclear. The expression of smooth muscle alpha-actin (SMalphaA) is the most characteristic feature of myofibroblasts; therefore, it was speculated that any factors that promote SMalphaA expression might be the key to transdifferentiation to myofibroblasts and disease exacerbation. A transcription factor CCAAT/enhancer-binding protein delta (C/EBPdelta) was identified and demonstrated to bind to sequences including the CArG motif from SMalphaA intron 1 and to increase transcriptional activity of this promoter. Expression of SMalphaA and C/EBPdelta in the glomerular area was upregulated in rat anti-Thy1 glomerulonephritis and mouse Habu-venom glomerulonephritis, both of which are models of mesangioproliferative glomerulonephritis. In the latter model, C/EBPdelta knockout mice demonstrated significantly less SMalphaA expression in the glomerular area on day 8 and less renal functional deterioration on day 14, compared with wild-type...Continue Reading

Citations

Oct 25, 2013·International Journal of Biological Sciences·Kuppusamy Balamurugan, Esta Sterneck
Feb 7, 2007·International Review of Cytology·Ian A Darby, Tim D Hewitson
Jul 29, 2006·The Journal of Biological Chemistry·Muthusamy ThangarajuVadivel Ganapathy
Nov 20, 2013·Laboratory Investigation; a Journal of Technical Methods and Pathology·JanWillem DuitmanC Arnold Spek
Nov 9, 2006·The Journal of Biological Chemistry·Masanobu TakejiTakeshi Miwa
Mar 27, 2021·Molecular Therapy. Methods & Clinical Development·Qingwei WangLian-Wang Guo

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