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

We analyzed mRNAs that were up- or down-regulated in fibroblasts from Werne r syndrome (WS) patients compared with those from normal individuals. The m RNAs from normal and WS cells were first screened by differential display, and those mRNAs that were apparently up- or down-regulated were selected ex cept for mRNAs related to extra-cellular matrix (ECM) proteins that are alr eady known to be up-regulated in WS fibroblasts. Then, the expression level s of these mRNAs were semiquantified by northern blot analysis, and six up- regulated and two down-regulated mRNAs were identified in WS cell lines. Am ong the six up-regulated mRNAs were three mRNAs that coded TGF beta-1 and t wo 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 acceler ated cellular senescence of fibroblasts of WS patients. (C) 2000 Elsevier S cience Ireland Ltd. All rights reserved.