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Colla corii asini might upregulate ZNF471 and THOC5 by KRAB domain–containing zinc-finger protein pathway and THO complex subunit 5 pathway to improve anemia of pregnant women with β-thalassemia

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Abstract

Pregnant patients with β-thalassemia are more likely to have progressive anemia which expose them to risk of adverse pregnancy outcomes, blood transfusion, and iron overload. Results from our previous study indicated that Colla corii asini (CCA, E’jiao), a natural ingredient of traditional Chinese medicine, could significantly increase hemoglobin level of pregnant women with β- thalassemia, but the underlying molecular mechanism was unclear. Thus, we applied high-throughput transcriptome sequencing to study the transcriptomic change before and after the CCA treatment. Twenty eligible pregnant women were recruited and randomized to either the CCA treatment group or the blank control group in a 3:1 ratio. Patients in the treatment group orally received daily 15 g CCA powder for 4 weeks. We analyzed the therapeutic effect indexes and the transcriptomic change in subjects’ peripheral blood before and after treatment. We found that β CD 41-42(-TTCT)/βA was the main genotype of the subjects. The regulatory impact of CCA treatment became more evident among the subjects of genotype β CD 41-42(-TTCT)/βA. Gene ontogenesis analysis revealed that the top five molecular functions of differentially expressed genes were involved in membrane functionality and cellular structure. We further identified two consistent upregulated genes ZNF471 and THOC5 in the effective treatment group, which were engaged in Kruppel-associated box (KRAB) domain-containing zinc-finger protein pathway and THOC5 pathway, respectively. Based on our current findings, we hypothesize that the anti-anemia effect of CCA on pregnant women with β-thalassemia might be related to translation regulation of spectrin synthesis, membrane stability, and eventually prolonged the life span of erythrocytes.

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Funding

This study was supported by the Science and Technology Project of Guangdong Province (grant no. 2017ZC0150) and by grants from the National Natural Science Foundation of China (grant no. 81704111).

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Authors and Affiliations

  1. Department of Obstetrics, the First Affiliated Hospital, Guangzhou University of Chinese Medicine, Guangzhou, China

    Yanfang Li, Xiangyi Li, Jingwen Zhou & Daocheng Li

  2. Department of Clinical Laboratory, the First Affiliated Hospital, Guangzhou University of Chinese Medicine, Guangzhou, China

    Zhanfeng Zhang

  3. Department of Gynecology, the First Affiliated Hospital, Guangzhou University of Chinese Medicine, Guangzhou, China

    Lilin Yang

  4. First School of Clinical Medicine, Guangzhou University of Chinese Medicine, No.12 Jichang Road, Guangzhou, 510405, Guangdong, China

    Songping Luo

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  1. Yanfang Li
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  2. Zhanfeng Zhang
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  4. Xiangyi Li
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  5. Jingwen Zhou
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Correspondence to Songping Luo.

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The procedures performed in the study were approved by the local ethics committee and were conducted in accordance with the current version of the Declaration of Helsinki.

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Li, Y., Zhang, Z., Yang, L. et al. Colla corii asini might upregulate ZNF471 and THOC5 by KRAB domain–containing zinc-finger protein pathway and THO complex subunit 5 pathway to improve anemia of pregnant women with β-thalassemia. Ann Hematol 98, 1813–1826 (2019). https://doi.org/10.1007/s00277-019-03710-1

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  • DOI: https://doi.org/10.1007/s00277-019-03710-1

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