Protein-tyrosine phosphatases in the vessel wall: differential expression after acute arterial injury.
Protein-tyrosine phosphatases in the vessel wall: differential expression after acute arterial injury.
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DOI：
10.1161/01.atv.20.5.1189
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发表时间：
2000-05
期刊：
影响因子：
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通讯作者：
M. Wright;R. Seifert;D. Bowen-Pope
中科院分区：
文献类型：
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作者：
M. Wright;R. Seifert;D. Bowen-Pope
许多蛋白酪氨酸磷酸酶（PTPases）现已被确定，但很少有人知道PTPases在血管组织和血管疾病中的表达和调节。聚合酶链反应（PCR）扩增和PTPases催化结构域的cDNA指纹图谱，结合PCR产物文库的随机测序，在大鼠颈动脉中鉴定了18种（8种受体样和10种胞质）PTPases，并揭示了其中5种PTPases在球囊导管损伤后新生内膜形成过程中的差异表达。采用原位杂交技术对5种差异表达PTPases的血管横截面mRNA表达进行定位。这表明，对于3种PTP酶（SHP 1、CD 45和PTP β），差异转录物丰度是由于表达它们的细胞类型的出现/丢失（SHP 1和CD 45为白细胞，PTP β为内皮细胞）。然而，2 PTPases（PTPL 1和PTP 1B）的mRNA表达特异性上调增殖和迁移的平滑肌细胞（SMC）的特征性时间和区域模式，以响应血管损伤。定量PCR分析表明，PTP 1B和PTPL 1诱导约30倍和约60倍，分别在损伤后2周，在受损的血管相比，未受伤的血管。PTP 1B在血管损伤后的中膜中迅速上调，并在新生内膜中保持高表达。相比之下，PTPL 1的表达并没有显着增加，直到SMC已经迁移到内膜。PTP 1B和PTPL 1在损伤后SMC的差异表达表明这些PTPases在血管壁重塑的调节中的作用。
Many protein-tyrosine phosphatases (PTPases) have now been identified, but little is known about PTPase expression and regulation in vascular tissue and in vascular disease. Polymerase chain reaction (PCR) amplification and cDNA fingerprinting of PTPase catalytic domains, combined with random sequencing of PCR product libraries, identified 18 (8 receptor-like and 10 cytosolic) PTPases in the rat carotid artery and revealed differential expression of 5 of these PTPases during neointima formation after balloon catheter injury. In situ hybridization was used to localize mRNA expression in vessel cross sections for the 5 differentially expressed PTPases. This revealed that for 3 PTPases (SHP1, CD45, and PTPbeta), differential transcript abundance was due to appearance/loss of the cell types by which they were expressed (leukocytes for SHP1 and CD45, endothelial cells for PTPbeta). However, mRNA expression of 2 PTPases (PTPL1 and PTP1B) was specifically upregulated by proliferating and migrating smooth muscle cells (SMCs) in characteristic temporal and regional patterns in response to vessel damage. Quantitative PCR analysis showed that PTP1B and PTPL1 were induced approximately 30-fold and approximately 60-fold, respectively, by 2 weeks after injury in the damaged vessels compared with the uninjured vessels. PTP1B was rapidly upregulated in the media after vessel injury and remained highly expressed in the developing neointima. By contrast, PTPL1 expression did not increase dramatically until the SMCs had migrated into the intima. The differential expression of PTP1B and PTPL1 by SMCs after injury suggests roles for these PTPases in the regulation of vessel wall remodeling.