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Abnormal tracheal cartilage formation in mice lacking Cav3.2 T‐type Ca 2+ channels (540.3)
Author(s) -
Lin ShinShiou,
Tzeng BingHsiean,
Lee KuanRong,
Smith Richard,
Campbell Kevin,
Chen ChienChang
Publication year - 2014
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.28.1_supplement.540.3
Subject(s) - nfat , chondrogenesis , calcineurin , sox9 , chemistry , microbiology and biotechnology , downregulation and upregulation , endocrinology , medicine , transcription factor , biology , mesenchymal stem cell , gene , biochemistry , transplantation
Ca 2+ influx is crucial in initiating the differentiation of mesenchymal cells into chondrocytes, but which Ca 2+ channels are involved remains uncertain. Here we show that the T‐type voltage‐gated Ca 2+ channel Ca v 3.2 is essential for tracheal chondrogenesis. Mice lacking this channel (Ca v 3.2 ‐/‐ ) showed congenital tracheal stenosis because of incomplete formation of cartilaginous tracheal support. Conversely, Ca v 3.2 overexpression in ATDC5 cells enhanced chondrogenesis, which could be blunted by both blocking T‐type Ca 2+ channels and inhibiting calcineurin and suggests that Ca v 3.2 is responsible for Ca 2+ influx during chondrogenesis. Finally, the expression of sex‐determination region of Y chromosome (SRY)‐related high mobility group‐Box gene 9 (Sox9) was reduced in Ca v 3.2 ‐/‐ tracheas. Ca v 3.2‐dependent Sox9 upregulation required a putative nuclear factor of activated T cell (NFAT) binding site identified within the mouse Sox9 promoter. The signaling pathway underlying Ca 2+ ‐induced chondrogenesis involves the Ca v 3.2 T‐type channel and depends on calcineurin and NFAT.