WP1991 - SRF and miRs in smooth muscle differentiation and proliferation - Homo sapiens

Smooth muscle cells exhibit a unique plasticity, in that they are able to oscillate between proliferative and more quiescent, differentiated states. These two states are determined, in part, by a network of transcription factors, including Klf-4, Elk-1 and serum response factor (SRF), that regulate expression of genes controlling smooth muscle cell status. Two smooth muscle-enriched, co-transcribed microRNAs (miRNAs), miR-143 and miR-145, cooperatively target this transcription factor network to promote smooth muscle cell differentiation. miR-145 also acts in a positive feed-foward regulatory loop to enhance expression of the smooth muscle regulator, Myocardin (Myocd), which cooperates with SRF to activate transcription of miR-143/145. Conversely, the cardiac and skeletal muscle-enriched miRNA, miR-133, which is also under transcriptional control of both SRF and Mef2C, acts in a negative feed-back loop to decrease SRF translation. Other miRNAs, including miR-214 and miR-199a, also target SRF, limiting its activity in specific cell types.