Uchida Masashi, Suzuki Saki, Suzuki Takaaki, Ishii Itsuko
Division of Pharmacy, Chiba University Hospital, 1-8-1 Inohana, Chuo-ku, Chiba 260-8677, Japan.
Graduate School of Pharmaceutical Sciences, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba 260-8675, Japan.
Microvasc Res. 2016 Jan;103:36-40. doi: 10.1016/j.mvr.2015.10.003. Epub 2015 Oct 29.
The proliferation of vascular smooth muscle cells (SMCs) contributes to atherosclerotic plaque formation and restenosis. Cyclin-dependent kinase inhibitors, such as p27(Kip1) and p21(Cip1), are known to play significant roles in the control of the aberrant proliferation of SMCs. Primary cultured SMCs stop proliferating immediately when cultured in three-dimensional matrices of type-I collagen "honeycombs" structures. To clarify whether p27(Kip1) and p21(Cip1) are involved in the proliferative inhibition of SMCs cultured in honeycombs, the characteristics of SMCs derived from the aorta of both wild-type mice (p27[+/+] SMCs) and p27(Kip1) knockout mice (p27[-/-] SMCs) were investigated. Although the growth of p27(-/-) SMCs cultured on plates was faster than that of p27(+/+) SMCs, the number of both p27(+/+) and p27(-/-) SMCs did not change when they were cultured in honeycombs. p21(Cip1) expression was decreased but maintained in p27(-/-) SMCs cultured on plates and in honeycombs. Knockdown of p21(Cip1) in p27(-/-) SMCs promoted proliferation on plates. On the contrary, p21(Cip1) knockdown had no effect on the proliferation of p27(-/-) SMCs cultured in honeycombs. In conclusion, p27(Kip1) and p21(Cip1) are insufficient for the proliferative inhibition of SMCs cultured in honeycombs.
血管平滑肌细胞（SMC）的增殖会导致动脉粥样硬化斑块形成和再狭窄。已知细胞周期蛋白依赖性激酶抑制剂，如p27（Kip1）和p21（Cip1），在控制SMC异常增殖中发挥重要作用。原代培养的SMC在I型胶原蛋白“蜂窝”结构的三维基质中培养时会立即停止增殖。为了阐明p27（Kip1）和p21（Cip1）是否参与了在蜂窝结构中培养的SMC的增殖抑制，研究了野生型小鼠主动脉来源的SMC（p27[+/+] SMC）和p27（Kip1）基因敲除小鼠主动脉来源的SMC（p27[-/-] SMC）的特性。虽然在平板上培养的p27（-/-）SMC的生长速度比p27（+/+）SMC快，但当它们在蜂窝结构中培养时，p27（+/+）和p27（-/-）SMC的数量均未改变。在平板上和蜂窝结构中培养的p27（-/-）SMC中，p21（Cip1）表达降低但仍维持。在p27（-/-）SMC中敲低p21（Cip1）可促进其在平板上的增殖。相反，敲低p21（Cip1）对在蜂窝结构中培养的p27（-/-）SMC的增殖没有影响。总之，p27（Kip1）和p21（Cip1）不足以抑制在蜂窝结构中培养的SMC的增殖。
