2. Academic Validation
  3. Downregulation of CD151 induces oxidative stress and apoptosis in trophoblast cells via inhibiting ERK/Nrf2 signaling pathway in preeclampsia

Downregulation of CD151 induces oxidative stress and apoptosis in trophoblast cells via inhibiting ERK/Nrf2 signaling pathway in preeclampsia

  • Free Radic Biol Med. 2021 Feb 20;164:249-257. doi: 10.1016/j.freeradbiomed.2020.12.441.
Zhiyin Wang 1,  Bin Cai 2,  Chenrui Cao 3,  Haining Lv 3,  Yimin Dai 3,  Mingming Zheng 3,  Guangfeng Zhao 3,  Yanfang Peng 3,  Wenjing Gou 3,  Jingmei Wang 4,  Dan Liu 5,  Yali Hu 6
Affiliations

Affiliations

  • 1 Department of Obstetrics and Gynecology, Drum Tower Clinical Medical College, Nanjing Medical University, Nanjing, China.
  • 2 Department of Obstetrics and Gynecology, Nanjing Drum Tower Hospital Clinical College of Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, China.
  • 3 Department of Obstetrics and Gynecology, Nanjing Drum Tower Hospital, Nanjing University Medical School, Nanjing, China.
  • 4 Department of Pathology, Nanjing Drum Tower Hospital, Nanjing University Medical School, Nanjing, China. Electronic address: jingmei026@126.com.
  • 5 Department of Obstetrics and Gynecology, Nanjing Drum Tower Hospital, Nanjing University Medical School, Nanjing, China. Electronic address: liudan870718@126.com.
  • 6 Department of Obstetrics and Gynecology, Drum Tower Clinical Medical College, Nanjing Medical University, Nanjing, China; Department of Obstetrics and Gynecology, Nanjing Drum Tower Hospital Clinical College of Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, China. Electronic address: yalihu@nju.edu.cn.
PMID: 33450381 DOI: 10.1016/j.freeradbiomed.2020.12.441
Abstract

Preeclampsia (PE) is a pregnancy-related syndrome characterized by new-onset hypertension and proteinuria after gestational 20 weeks. Oxidative stress, resulting from the imbalance between the production of oxidants and antioxidants in placentas, is recognized as a key pathology of PE. To date, the molecules that regulate antioxidants production remain unclear. CD151, a member of tetraspanins, is an important regulator of many physiological functions. However, the function of CD151 in oxidative stress and its association with pregnancy-related complications are currently unknown. In the present study, we have demonstrated that CD151 was a key regulator of antioxidants in placentas. Compared with the placentas of the controls, the placentas of PE patients exhibited decreased CD151 expression accompanying with decreased antioxidant gene expression (HO-1, NQO-1, GCLC and SOD-1). In vitro, overexpression of CD151 in trophoblast cells could enhance HO-1, NQO-1, GCLC and SOD-1 expression but downregulation of CD151 decreased those antioxidant genes expression, which indicates CD151 is the upstream of antioxidants. Importantly, the phenotype of PE (hypertension and proteinuria) was mimicked in the downregulating CD151 induced mouse model. Moreover, the beneficial effect of CD151 in trophoblast cells was hindered when ERK and Nrf2 signaling were blocked. Overall, our results revealed CD151 might be a new target for PE treatment.

Keywords

Antioxidant; Apoptosis; CD151; Oxidative stress; PE; Trophoblast.

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