Calcium Signaling T-type Calcium Channels Involved In Collagen Fragment-Induced Smooth Muscle Cell Death

International audienceApoptosis of smooth muscle cells (SMC) due to changes in extracellular matrix has emerged as an important factor underlying vascular and visceral disease progression. The calcium signal induced by extracellular matrix fragmentation also plays a pivotal role in cell death and disease evolution. Here, we found that KDGEA, a particular motif of type I collagen, induced rat duodenal SMC death in cultures through specific interaction with α 2 β 1 integrin signaling as suggested by (1) the absence of KDGAA effect, an inactive analog of KDGEA, or LDV, a fibronectin fragment that recognizes α 4 β 1 integrin, and (2) the inhibition of SMC death induced by KDGEA when α 2 β 1 expression was knocked down by antisense oligonucleotide. DNA fragmentation was also detected in KDGEA-treated cells, thus suggesting activation of an apoptotic process. These KDGEA-activated processes were totally blunted by pharmacological modulation of Ca 2+ entry through T-type Ca 2+ channels and antisense oligonucleotides directed against these channels. KDGEA also increased caffeine-induced calcium release and this effect was abolished when cultures were treated with either antisense oligonucleotide or T-type channel blockers. These results suggested that type I collagen peptide KDGEA can induce the death of SMC through T-type Ca 2+ channel activation and alteration of calcium release from sarcoplasmic reticulum