| First Author | Zhao L | Year | 2013 |
| Journal | Am J Physiol Lung Cell Mol Physiol | Volume | 305 |
| Issue | 6 | Pages | L409-18 |
| PubMed ID | 23831617 | Mgi Jnum | J:210114 |
| Mgi Id | MGI:5569575 | Doi | 10.1152/ajplung.00032.2013 |
| Citation | Zhao L, et al. (2013) Transdifferentiation of alveolar epithelial type II to type I cells is controlled by opposing TGF-beta and BMP signaling. Am J Physiol Lung Cell Mol Physiol 305(6):L409-18 |
| abstractText | Alveolar epithelial type II (ATII) cells are essential for maintaining normal lung homeostasis because they produce surfactant, express innate immune proteins, and can function as progenitors for alveolar epithelial type I (ATI) cells. Although autocrine production of transforming growth factor (TGF)-beta1 has been shown to promote the transdifferentiation of primary rat ATII to ATI cells in vitro, mechanisms controlling this process still remain poorly defined. Here, evidence is provided that Tgf-beta1, -2, -3 mRNA and phosphorylated SMAD2 and SMAD3 significantly increase as primary cultures of mouse ATII cells transdifferentiate to ATI cells. Concomitantly, bone morphogenetic protein (Bmp)-2 and -4 mRNA, and phosphorylated SMAD1/5/8 expression decrease. Exogenously supplied recombinant human TGF-beta1 inhibited BMP signaling and enhanced transdifferentiation by promoting the loss of ATII cell-specific gene expression and weakly stimulating ATI cell-specific gene expression. On the other hand, exogenously supplied recombinant human BMP-4 inhibited TGF-beta signaling and delayed transdifferentiation by inhibiting the gain in ATI cell-specific gene expression and weakly delaying the loss of ATII cell-specific gene expression. In mouse lung epithelial (MLE15) cells, small-interfering RNA (siRNA) knockdown of TGF-beta receptor type-1 enhanced basal expression of ATII genes while siRNA RNA knockdown of BMP receptors type-1a and -1b enhanced basal expression of ATI genes. Together, these results suggest that the rate of ATII cell transdifferentiation is controlled by the opposing actions of BMP and TGF-beta signaling that switch during the process of transdifferentiation. |
