Linking phospholipase C isoforms with differentiation function in human vascular smooth muscle cells

The phosphoinositol-phospholipase C (PLC) family of enzymes consists of a number of isoforms, each of whichhas different cellular functions. PLCγ1 is primarily linked to tyrosine kinase transduction pathways, whereasPLCδ1 has been associatedwith a number of regulatory proteins, including those controlling the cell cycle. Recentstudies have shown a central role of PLC in cell organisation and in regulating a wide array of cellular responses. Itis of importance to define the precise role of each isoform, and how this changes the functional outcome of thecell. Here we investigated differences in PLC isoform levels and activity in relation to differentiation of humanand rat vascular smooth muscle cells. Using Western blotting and PLC activity assay, we show that PLCδ1 andPLCγ1 are the predominant isoforms in randomly cycling human vascular smooth muscle cells (HVSMCs).Growth arrest of HVSMCs for seven days of serum deprivation was consistently associated with increases inPLCδ1 and SM α-actin, whereas there were no changes in PLCγ1 immuno-reactivity. Organ culture of rat mesentericarteries in serumfreemedia (SFM), a model of de-differentiation, led to a loss of contractility aswell as a lossof contractile proteins (SM α-actin and calponin) and PLCδ1, and no change in PLCγ1 immuno-reactivity. Takentogether, these data indicate that PLCδ1 is the predominant PLC isoform in vascular smooth muscle, and confirmthat PLCδ1 expression is affected by conditions that affect the cell cycle, differentiation status and contractilefunction