Elevated GABRP Expression is Correlated to the Excessive Autophagy in Intrahepatic Cholestasis of Pregnancy

Overview

Journal Heliyon

Specialty Social Sciences

Date 2023 Feb 7

PMID 36747550

Authors

Ruihong Dong

Yayi Hu

Qian Chen

Dan Shan

Yuxia Wu

Affiliations

Soon will be listed here.

Abstract

Methods: A total of 27 participants, including 18 ICP patients and 9 healthy pregnancies were recruited according to strict inclusion criteria. Placentas of ICP patients and controls were collected immediately after cesarean section before labor onset. GABRP and autophagic markers expression in placenta were investigated by immunohistochemistry (IHC), RT-qPCR, and Western blot.

Results: The neonatal birthweight and gestational weeks were significantly lower in severe ICP group, while the hepatic enzymes were elevated in ICP group. Semiquantitative analysis of IHC revealed the AOD of GABRP in severe ICP patients was higher than that in mild ICP patients and control pregnancies. Western blot and RT-qPCR analysis both indicated that the expression of GABRP and ATG14 were significantly elevated in severe ICP patients. Moreover, GABRP was correlated with TBA (r = 0.64, < 0.05), ATG14 (r = 0.87, < 0.05), direct bilirubin (r = 0.54, < 0.05), ALT (r = 0.72, < 0.05), and AST (r = 0.67, < 0.05).

Conclusion: There were elevated expression of GABRP, ATG14 and LC3 in ICP placentas compared with uncomplicated pregnancies. The expression of GABRP was associated with autophagy and was correlated with the TBA levels.

Citing Articles

A diagnostic signatures for intervertebral disc degeneration using TNFAIP6 and COL6A2 based on single-cell RNA-seq and bulk RNA-seq analyses.

Song H, Li Z, Huang Q, Wu C, Li M, Shen J Ann Med. 2024; 57(1):2443568.

PMID: 39704340 PMC: 11703038. DOI: 10.1080/07853890.2024.2443568.

LC-MS/MS untargeted lipidomics uncovers placenta lipid signatures from intrahepatic cholestasis of pregnancy.

Xiong L, Tang M, Liu H, Cai J, Jin Y, Huang C Front Physiol. 2024; 15:1276722.

PMID: 38887316 PMC: 11180999. DOI: 10.3389/fphys.2024.1276722.

Hepatoprotective effects of aspirin on diethylnitrosamine-induced hepatocellular carcinoma in rats by reducing inflammation levels and PD-L1 expression.

Wang Y, Wang M, Liu C, Hao M, Wang W, Li Y Sci Rep. 2023; 13(1):21362.

PMID: 38049630 PMC: 10695938. DOI: 10.1038/s41598-023-48812-z.

References

Jiang S, Zhu L, Zhang M, Li R, Yang Q, Yan J . GABRP regulates chemokine signalling, macrophage recruitment and tumour progression in pancreatic cancer through tuning KCNN4-mediated Ca signalling in a GABA-independent manner. Gut. 2019; 68(11):1994-2006. DOI: 10.1136/gutjnl-2018-317479. View

Levine B, Kroemer G . Biological Functions of Autophagy Genes: A Disease Perspective. Cell. 2019; 176(1-2):11-42. PMC: 6347410. DOI: 10.1016/j.cell.2018.09.048. View

Oh S, Roh C . Autophagy in the placenta. Obstet Gynecol Sci. 2017; 60(3):241-259. PMC: 5439273. DOI: 10.5468/ogs.2017.60.3.241. View

Tanida I, Ueno T, Kominami E . LC3 and Autophagy. Methods Mol Biol. 2008; 445:77-88. DOI: 10.1007/978-1-59745-157-4_4. View

Nakashima A, Aoki A, Kusabiraki T, Cheng S, Sharma S, Saito S . Autophagy regulation in preeclampsia: Pros and cons. J Reprod Immunol. 2017; 123:17-23. DOI: 10.1016/j.jri.2017.08.006. View

Smith D, Rood K . Intrahepatic Cholestasis of Pregnancy. Clin Obstet Gynecol. 2019; 63(1):134-151. DOI: 10.1097/GRF.0000000000000495. View

Sung H, Yang S, Ju W, Ahn J . Aberrant epigenetic regulation of GABRP associates with aggressive phenotype of ovarian cancer. Exp Mol Med. 2017; 49(5):e335. PMC: 5454450. DOI: 10.1038/emm.2017.62. View

Shan D, Dong R, Hu Y . Current understanding of autophagy in intrahepatic cholestasis of pregnancy. Placenta. 2021; 115:53-59. DOI: 10.1016/j.placenta.2021.09.014. View

Geenes V, Chappell L, Seed P, Steer P, Knight M, Williamson C . Association of severe intrahepatic cholestasis of pregnancy with adverse pregnancy outcomes: a prospective population-based case-control study. Hepatology. 2013; 59(4):1482-91. PMC: 4296226. DOI: 10.1002/hep.26617. View

10.

Kim J, Kim Y, Lee H, Jin H, Neupane C, Kim S . GABAergic signaling linked to autophagy enhances host protection against intracellular bacterial infections. Nat Commun. 2018; 9(1):4184. PMC: 6180030. DOI: 10.1038/s41467-018-06487-5. View

11.

Williamson C, Geenes V . Intrahepatic cholestasis of pregnancy. Obstet Gynecol. 2014; 124(1):120-133. DOI: 10.1097/AOG.0000000000000346. View

12.

Glantz A, Marschall H, Mattsson L . Intrahepatic cholestasis of pregnancy: Relationships between bile acid levels and fetal complication rates. Hepatology. 2004; 40(2):467-74. DOI: 10.1002/hep.20336. View

13.

Chao S, Xiaojun L, Haizhen W, Ludi F, Shaozhen L, Zhiwen S . Lithocholic acid activates mTOR signaling inducing endoplasmic reticulum stress in placenta during intrahepatic cholestasis of pregnancy. Life Sci. 2019; 218:300-307. DOI: 10.1016/j.lfs.2018.12.050. View

14.

Lu J, Zhang Q, Tan D, Luo W, Zhao H, Ma J . GABA A receptor π subunit promotes apoptosis of HTR-8/SVneo trophoblastic cells: Implications in preeclampsia. Int J Mol Med. 2016; 38(1):105-12. PMC: 4899026. DOI: 10.3892/ijmm.2016.2608. View

15.

Diao J, Liu R, Rong Y, Zhao M, Zhang J, Lai Y . ATG14 promotes membrane tethering and fusion of autophagosomes to endolysosomes. Nature. 2015; 520(7548):563-6. PMC: 4442024. DOI: 10.1038/nature14147. View

16.

Chua H, Chebib M . GABA Receptors and the Diversity in their Structure and Pharmacology. Adv Pharmacol. 2017; 79:1-34. DOI: 10.1016/bs.apha.2017.03.003. View

17.

Wei W, Hu Y . Expression of hypoxia-regulated genes and glycometabolic genes in placenta from patients with intrahepatic cholestasis of pregnancy. Placenta. 2014; 35(9):732-6. DOI: 10.1016/j.placenta.2014.06.372. View

18.

Nakashima A, Tsuda S, Kusabiraki T, Aoki A, Ushijima A, Shima T . Current Understanding of Autophagy in Pregnancy. Int J Mol Sci. 2019; 20(9). PMC: 6539256. DOI: 10.3390/ijms20092342. View

19.

Raz Y, Lavie A, Vered Y, Goldiner I, Skornick-Rapaport A, Landsberg Asher Y . Severe intrahepatic cholestasis of pregnancy is a risk factor for preeclampsia in singleton and twin pregnancies. Am J Obstet Gynecol. 2015; 213(3):395.e1-8. DOI: 10.1016/j.ajog.2015.05.011. View

20.

Li X, Wang H, Yang X, Wang X, Zhao L, Zou L . GABRP sustains the stemness of triple-negative breast cancer cells through EGFR signaling. Cancer Lett. 2021; 514:90-102. DOI: 10.1016/j.canlet.2021.04.028. View