Altered expression of leptin and leptin receptor in the development of immune‑mediated aplastic anemia in mice

Yin,Xiangcong; Yang,Jie; Liu,Yuhua; Zhang,Jian; Xin,Chunlei; Zhao,Hongguo; Wang,Wei; Shi,Xue; Cui,Zhongguang; Li,Guanglun; Zhao,Chunting; Liu,Xiaodan

doi:10.3892/etm.2019.7660

Altered expression of leptin and leptin receptor in the development of immune‑mediated aplastic anemia in mice

Authors:
- Xiangcong Yin
- Jie Yang
- Yuhua Liu
- Jian Zhang
- Chunlei Xin
- Hongguo Zhao
- Wei Wang
- Xue Shi
- Zhongguang Cui
- Guanglun Li
- Chunting Zhao
- Xiaodan Liu
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Affiliations: Hematology Diagnosis Laboratory, The Affiliated Hospital of Qingdao University, Qingdao, Shandong 266003, P.R. China, Department of Medicine, Qingzhou Traditional Chinese Medicine Hospital, Weifang, Shandong 262500, P.R. China, Department of Hematology, Rizhao People's Hospital, Rizhao, Shandong 276800, P.R. China, Department of Hematology, Jining No. 1 People's Hospital, Jining, Shandong 272011, P.R. China, Department of Hematology, The Affiliated Hospital of Qingdao University, Qingdao, Shandong 266003, P.R. China
Published online on: June 11, 2019 https://doi.org/10.3892/etm.2019.7660
Pages: 1047-1056
Copyright: © Yin et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

The current study aimed to explore the levels of leptin (LEP) and LEP receptor (LEP‑R) on the progression of aplastic anemia (AA) with bone marrow fat conversion. An AA model was developed by infusing C57BL/6 lymph node cells into BALB/c mice. At 0, 3, 6, 9, 12, 15 and 18 days after modeling, routine blood counts, bone marrow biopsy slides, lymphocyte subsets (CD4+ and CD8+ T cells) and cytokine levels [including interleukin (IL)‑2, IL‑4, IL‑5 and interferon‑γ] were assessed. LEP and LEP‑R levels in peripheral blood serum, mesenchymal stem cells (MSCs) and bone marrow were also analyzed by enzyme‑linked immunosorbent assay, polymerase chain reaction and immunohistochemistry. The relevance of LEP, LEP‑R and other factors was analyzed by Pearson's correlation analysis. Peripheral pancytopenia (reduced count of white blood cells, red blood cells, hemoglobin and platelets), abnormal immune factor levels and histological changes in bone marrow sections were detected in the AA model mice, suggesting that these mice mimicked the pathological changes commonly observed in AA. In addition, following the establishment of AA, the LEP level was gradually increased and the LEP‑R level was reduced in the mice over time (P<0.05). The expression of adipogenic genes, including CCAAT/enhancer‑binding protein (C/EBP)α, C/EBPβ and peroxisome proliferator‑activated receptor γ, was markedly increased, while the expression of the osteogenic gene runt‑related transcription factor 2 was reduced compared with the levels in the control group (P<0.05). Taken together, damage to LEP‑R may lead to dysregulation of LEP and the enhancement of MSCs to differentiate into adipocytes, resulting in excessive fat in bone marrow of AA patients.

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