Overexpression of mRNAs of TGFβ-1 and related genes in fibroblasts of Werner syndrome patients

We analyzed mRNAs that were up- or down-regulated in fibroblasts from Werner syndrome (WS) patients compared with those from normal individuals. The mRNAs from normal and WS cells were first screened by differential display, and those mRNAs that were apparently up- or down-regulated were selected except for mRNAs related to extra-cellular matrix (ECM) proteins that are already known to be up-regulated in WS fibroblasts. Then, the expression levels of these mRNAs were semiquantified by northern blot analysis, and six up-regulated and two down-regulated mRNAs were identified in WS cell lines. Among the six up-regulated mRNAs were three mRNAs that coded TGF beta-1 and two proteins, their expressions of which were increased by TGF beta-1. These results together with the fact that TGF beta-1 up-regulates the expression of ECM proteins strongly suggest that TGF beta-1 has a key role in accelerated cellular senescence of fibroblasts of WS patients. (C) 2000 Elsevier Science Ireland Ltd. All rights reserved.