| First Author | Shen J | Year | 2011 |
| Journal | Cardiovasc Res | Volume | 90 |
| Issue | 1 | Pages | 28-37 |
| PubMed ID | 21183509 | Mgi Jnum | J:186022 |
| Mgi Id | MGI:5430847 | Doi | 10.1093/cvr/cvq378 |
| Citation | Shen J, et al. (2011) Arterial injury promotes medial chondrogenesis in Sm22 knockout mice. Cardiovasc Res 90(1):28-37 |
| abstractText | AIMS: Expression of SM22 (also known as SM22alpha and transgelin), a vascular smooth muscle cells (VSMCs) marker, is down-regulated in arterial diseases involving medial osteochondrogenesis. We investigated the effect of SM22 deficiency in a mouse artery injury model to determine the role of SM22 in arterial chondrogenesis. METHODS AND RESULTS: Sm22 knockout (Sm22(-/-)) mice developed prominent medial chondrogenesis 2 weeks after carotid denudation as evidenced by the enhanced expression of chondrogenic markers including type II collagen, aggrecan, osteopontin, bone morphogenetic protein 2, and SRY-box containing gene 9 (SOX9). This was concomitant with suppression of VSMC key transcription factor myocardin and of VSMC markers such as SM alpha-actin and myosin heavy chain. The conversion tendency from myogenesis to chondrogenesis was also observed in primary Sm22(-/-) VSMCs and in a VSMC line after Sm22 knockdown: SM22 deficiency altered VSMC morphology with compromised stress fibre formation and increased actin dynamics. Meanwhile, the expression level of Sox9 mRNA was up-regulated while the mRNA levels of myocardin and VSMC markers were down-regulated, indicating a pro-chondrogenic transcriptional switch in SM22-deficient VSMCs. Furthermore, the increased expression of SOX9 was mediated by enhanced reactive oxygen species production and nuclear factor-kappaB pathway activation. CONCLUSION: These findings suggest that disruption of SM22 alters the actin cytoskeleton and promotes chondrogenic conversion of VSMCs. |
