Ha Joong Gyu, Li Lan, Lee Dong heon, Na Sung hun, Ha Kwon Soo, Kim Young-Myeong, Ko Jung Hwa, Hwang Jong Yun
Department of Obstetrics and Gynecology, Eulji University Hospital, Daejeon, Korea.
Department of Obstetrics and Gynecology, Kangwon National University School of Medicine, Chuncheon, Korea.
Reprod Sci. 2015 Dec;22(12):1530-8. doi: 10.1177/1933719115589415. Epub 2015 Jun 2.
Abnormal spiral artery remodeling during early pregnancy leads to preeclampsia. The proliferation and invasion of trophoblasts in pregnancy are important for spiral artery remodeling. This study examined whether heme oxygenase (HO) by-products (carbon monoxide biliverdin, and iron) play roles in regulating the restoration of proliferation and invasion of human umbilical vein endothelial cells (HUVECs), HTR-8/SV-neo cells originating from first-trimester trophoblasts, 3A(tPA 30-1) obtained from term trophoblasts, and human endometrial stromal cells (HESCs) inhibited by zinc protoporphyrin IX (Znpp-9).
We explored whether HO by-products restored the proliferation and invasion of HUVECs, HTR-8/SVneo cells, 3A(tPA 30-1) cells, and HESCs inhibited by Znpp-9 depending on the oxygen concentration.
Bilirubin promoted proliferation of HUVECs, HTR-8/SVneo cells, 3A(tPA-30-1) cells, and HESCs under both hypoxic and normoxic conditions. Biliverdin also promoted invasion of HUVECs, HTR-8/SVneo cells, 3A(tPA30-1) cells, and HESCs under both hypoxic and normoxic conditions. Carbon monoxide-releasing molecule 2 promoted the proliferation and invasion of specific cell types depending on the oxygen concentration.
Our data suggest that HO by-products differentially stimulate the proliferation and invasion of cells involved in pregnancy maintenance. When HO by-products are considered to be stimulants during the invasion and proliferation of such cells, both target cells and the gestational period should be considered.
妊娠早期螺旋动脉重塑异常会导致子痫前期。孕期滋养层细胞的增殖和侵袭对螺旋动脉重塑至关重要。本研究检测了血红素加氧酶（HO）的副产物（一氧化碳、胆红素和铁）在调节人脐静脉内皮细胞（HUVECs）、源自孕早期滋养层细胞的HTR-8/SV-neo细胞、源自足月滋养层细胞的3A(tPA 30-1)细胞以及受锌原卟啉IX（Znpp-9）抑制的人子宫内膜基质细胞（HESCs）的增殖和侵袭恢复中是否发挥作用。
我们探究了HO的副产物是否根据氧浓度恢复受Znpp-9抑制的HUVECs、HTR-8/SVneo细胞、3A(tPA 30-1)细胞和HESCs的增殖和侵袭。
胆红素在缺氧和常氧条件下均促进HUVECs、HTR-8/SVneo细胞、3A(tPA-30-1)细胞和HESCs的增殖。胆红素在缺氧和常氧条件下也均促进HUVECs、HTR-8/SVneo细胞、3A(tPA30-1)细胞和HESCs的侵袭。一氧化碳释放分子2根据氧浓度促进特定细胞类型的增殖和侵袭。
我们的数据表明，HO的副产物对参与维持妊娠的细胞的增殖和侵袭有不同的刺激作用。当将HO的副产物视为此类细胞侵袭和增殖过程中的刺激物时，应同时考虑靶细胞和妊娠期。
