M. Ekblom et al., DOWN-REGULATION OF TENASCIN EXPRESSION BY GLUCOCORTICOIDS IN BONE-MARROW STROMAL CELLS AND IN FIBROBLASTS, The Journal of cell biology, 123(4), 1993, pp. 1037-1045
Tenascin, a predominantly mesenchymal extracellular matrix (ECM) glyco
protein has a rather restricted tissue distribution, but until now fac
tors that inhibit its expression have not been identified. Glucocortic
oids are known to be beneficial for establishment of myelopoiesis in l
ong-term bone marrow cultures. Tenascin was found to be expressed in t
he bone marrow, and glucocorticoids were found to affect bone marrow t
enascin expression. Both tenascin mRNAs and the mRNA of another ECM pr
otein, laminin B1 chain, were drastically downregulated by glucocortic
oids during initiation of bone marrow cultures. However, in already es
tablished long-term cultures glucocorticoids did not affect laminin B1
chain mRNA levels although tenascin mRNAs continued to be downregulat
ed. Studies with a stromal cell line (MC3T3-G2/PA6) and fibroblasts (3
T3) suggested that glucocorticoids act directly on the stromal cells t
hat produce tenascin. In 3T3 cells this downregulation occurred within
12 h of glucocorticoid-treatment, suggesting that glucocorticoids act
ed through cis regulatory elements of the tenascin gene. We suggest th
at glucocorticoids in part regulate hematopoiesis by modifying the ECM
. Furthermore, downregulation of tenascin expression by glucocorticoid
s may in part explain the restricted tissue distribution of tenascin i
n other tissues.