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Periostin gene expression is regulated by the bHLH transcription factor TWIST2 in human skin fibroblasts
Author(s) -
Franco Hector,
Casasnovas José J,
Cadilla Carmen Lydia
Publication year - 2009
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.23.1_supplement.660.11
Subject(s) - periostin , transcription factor , gene knockdown , biology , microphthalmia associated transcription factor , microbiology and biotechnology , gene expression , gene , genetics , extracellular matrix
Periostin (POSTN), a cell adhesion protein involved in connective tissue development and maintenance, is regulated positively by the basic Helix‐Loop‐Helix (bHLH) transcription factor TWIST2. Two naturally occurring nonsense mutations of TWIST2 (Q119X and Q65X) were found in Puerto Rican and Omani Setleis Syndrome (SS) patients. The Yeast‐Two‐Hybrid assay was used to assay the dimerization properties of TWIST2 mutants. Wildtype and Q119X forms of TWIST2 form homodimers as well as heterodimers with E12 (a ubiquitous bHLH factor), while the Q65X TWIST2 mutant lacks ability to dimerize with itself and with E12. Microarray analysis of human skin fibroblasts suggests that TWIST2 seems to act as a positive regulator more frequently than as a repressor in human skin fibroblasts. POSTN is down‐regulated in SS patient fibroblasts when compared to normal controls, as confirmed by real time RT‐PCR. RNAi and TWIST2 over‐expression techniques provide evidence that POSTN is positively regulated by TWIST2. Knockdown of TWIST2 shows a decrease of POSTN expression over a 72hr time course in fibroblastic cells. Similarly, TWIST2 over‐expressed in these same cells results in increased POSTN expression over a similar time course. Overexpression of Twist2 in SS patient skin fibroblasts caused an increase in POSTN gene expression. This research is supported by MBRS RISE Grant R25GM061838, and RCMI Grant G12RR03051.