Heterogeneous nuclear ribonucleoprotein-H plays a suppressive role in visceral myogenesis

Mouse embryonic mesenchymal cells undergo spontaneous smooth muscle (SM) di fferentiation upon spreading/elongation in culture (Relan et al., J. Cell B iol. 147 (1999) 1341; Yang et al., Development 125 (1998) 2621; Yang et al. , Development 126 (1999) 3027). Using these cells we generated a subtracted cDNA library to identify potential suppressors of SM myogenesis. One of th e differentially expressed genes was heterogeneous nuclear ribonucleoprotei n-H (hnRNP-H), which is involved in pre-mRNA alternative splicing, hnRNP-H was highly expressed in mesenchymal cells prior to the onset of SM differen tiation, but its expression rapidly decreased in mesenchymal cells undergoi ng SM myogenesis. In vivo, the drop in hnRNP-H expression was restricted to visceral SM cells. Antisense oligodeoxynucleotide and antisense RNA were u sed to inhibit hnRNP-H synthesis in SM-differentiating mesenchymal cells an d in embryonic lung explants. A decrease in hnRNP-H levels resulted in upre gulation of SM-specific gene expression and increased bronchial SM developm ent in lung explants. hnRNP-H overexpression in cell cultures had the oppos ite effect. These studies, therefore, indicate a novel role for hnRNP-H in the control of visceral myogenesis. (C) 2001 Elsevier Science Ireland Ltd. All rights reserved.