Nie Ling, Zhao Jing-Hong, Wang Jiang, Song Rong, Zhu Shan-Jun
Department of Nephrology, Xinqiao Hospital, The Third Military Medical University, Chongqing 400037, China.
Department of Cardiovascular Disease, Xinqiao Hospital, The Third Military Medical University, Chongqing 400037, China.
Biomed Res Int. 2016;2016:2860516. doi: 10.1155/2016/2860516. Epub 2016 Sep 25.
Cardiac fibroblasts (CFs) play a key role in cardiac fibrosis by regulating the balance between extracellular matrix synthesis and breakdown. Although phosphatase and tensin homologue on chromosome 10 (PTEN) has been found to play an important role in cardiovascular disease, it is not clear whether PTEN is involved in functional regulation of CFs. In the present study, PTEN was overexpressed in neonatal rat CFs via recombinant adenovirus-mediated gene transfer. The effects of PTEN overexpression on cell-cycle progression and angiotensin II- (Ang II-) mediated regulation of collagen metabolism, synthesis of matrix metalloproteinases, and Akt/P27 signaling were investigated. Compared with uninfected cells and cells infected with green fluorescent protein-expressing adenovirus (Ad-GFP), cells infected with PTEN-expressing adenovirus (Ad-PTEN) significantly increased PTEN protein and mRNA levels in CFs ( < 0.05). The proportion of CFs in the G1/S cell-cycle phase was significantly higher for PTEN-overexpressing cells. In addition, Ad-PTEN decreased mRNA expression and the protein synthesis rate of collagen types I and III and antagonized Ang II-induced collagen synthesis. Overexpression of PTEN also decreased Ang II-induced matrix metalloproteinase-2 (MMP-2) and tissue inhibitor of metalloproteinase-1 (TIMP-1) production as well as gelatinase activity. Moreover, Ad-PTEN decreased Akt expression and increased P27 expression independent of Ang II stimulation. These results suggest that PTEN could regulate its functional effects in neonatal rat CFs partially via the Akt/P27 signaling pathway.
心脏成纤维细胞（CFs）通过调节细胞外基质合成与分解之间的平衡，在心脏纤维化中发挥关键作用。尽管已发现10号染色体上的磷酸酶和张力蛋白同源物（PTEN）在心血管疾病中起重要作用，但尚不清楚PTEN是否参与CFs的功能调节。在本研究中，通过重组腺病毒介导的基因转移，使新生大鼠CFs中PTEN过表达。研究了PTEN过表达对细胞周期进程以及血管紧张素II（Ang II）介导的胶原代谢调节、基质金属蛋白酶合成和Akt/P27信号传导的影响。与未感染细胞和感染绿色荧光蛋白表达腺病毒（Ad-GFP）的细胞相比，感染PTEN表达腺病毒（Ad-PTEN）的细胞中CFs的PTEN蛋白和mRNA水平显著升高（<0.05）。PTEN过表达细胞中处于G1/S细胞周期阶段的CFs比例显著更高。此外，Ad-PTEN降低了I型和III型胶原的mRNA表达及蛋白合成速率，并拮抗Ang II诱导的胶原合成。PTEN过表达还降低了Ang II诱导的基质金属蛋白酶-2（MMP-2）和金属蛋白酶组织抑制剂-1（TIMP-1）的产生以及明胶酶活性。此外，Ad-PTEN降低了Akt表达并增加了P27表达，且不依赖于Ang II刺激。这些结果表明，PTEN可能部分通过Akt/P27信号通路调节其在新生大鼠CFs中的功能作用。
