| First Author | Lin SS | Year | 2014 |
| Journal | Proc Natl Acad Sci U S A | Volume | 111 |
| Issue | 19 | Pages | E1990-8 |
| PubMed ID | 24778262 | Mgi Jnum | J:208830 |
| Mgi Id | MGI:5565092 | Doi | 10.1073/pnas.1323112111 |
| Citation | Lin SS, et al. (2014) Cav3.2 T-type calcium channel is required for the NFAT-dependent Sox9 expression in tracheal cartilage. Proc Natl Acad Sci U S A 111(19):E1990-8 |
| abstractText | Intracellular Ca(2+) transient is crucial in initiating the differentiation of mesenchymal cells into chondrocytes, but whether voltage-gated Ca(2+) channels are involved remains uncertain. Here, we show that the T-type voltage-gated Ca(2+) channel Cav3.2 is essential for tracheal chondrogenesis. Mice lacking this channel (Cav3.2(-/-)) show congenital tracheal stenosis because of incomplete formation of cartilaginous tracheal support. Conversely, Cav3.2 overexpression in ATDC5 cells enhances chondrogenesis, which could be blunted by both blocking T-type Ca(2+) channels and inhibiting calcineurin and suggests that Cav3.2 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), one of the earliest markers of committed chondrogenic cells, is reduced in Cav3.2(-/-) tracheas. Mechanistically, Ca(2+) influx via Cav3.2 activates the calcineurin/nuclear factor of the activated T-cell (NFAT) signaling pathway, and a previously unidentified NFAT binding site is identified within the mouse Sox9 promoter using a luciferase reporter assay and gel shift and ChIP studies. Our findings define a previously unidentified mechanism that Ca(2+) influx via the Cav3.2 T-type Ca(2+) channel regulates Sox9 expression through the calcineurin/NFAT signaling pathway during tracheal chondrogenesis. |
