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Int J Biol Sci 2022; 18(11):4469-4481. doi:10.7150/ijbs.72283 This issue Cite

Research Paper

The Low-density Lipoprotein Receptor-related Protein 6 Pathway in the Treatment of Intestinal Barrier Dysfunction Induced by Hypoxia and Intestinal Microbiota through the Wnt/β-catenin Pathway

Zhihua Liu1,2✉, Chao Li1,2, Min Liu1,2, Zhen Song1,2, Mary Pat Moyer3, Dan Su✉

1. Department of Anorectal Surgery, the Fifth Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong, 510799, China.
2. Key Laboratory of Biological Targeting Diagnosis, Therapy and Rehabilitation of Guangdong Higher Education Institutes, The Fifth Affiliated Hospital of Guangzhou Medical University.
3. INCELL Corporation, San Antonio, Texas, 78249, USA.
4. Department of Anorectal surgery. The Sixth Affiliated Hospital of Sun Yatsen University, Guangzhou 510665, China.

✉ Corresponding authors: Dan Su, MD, Department of Anorectal surgery. The Sixth Affiliated Hospital of Sun Yatsen University, Guangzhou 510665, China; Tel: +86-20-38250221; E-mail: sudan3sysu.edu.cn; Dr. Zhihua Liu, MD., Ph.D. Department of Cent More

Citation:
Liu Z, Li C, Liu M, Song Z, Moyer MP, Su D. The Low-density Lipoprotein Receptor-related Protein 6 Pathway in the Treatment of Intestinal Barrier Dysfunction Induced by Hypoxia and Intestinal Microbiota through the Wnt/β-catenin Pathway. Int J Biol Sci 2022; 18(11):4469-4481. doi:10.7150/ijbs.72283. https://www.ijbs.com/v18p4469.htm
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Abstract

Graphic abstract

Our study is to explore the key molecular of Low-density lipoprotein receptor-related protein 6 (LRP6) and the related Wnt/β-catenin pathway regulated by LRP6 during the intestinal barrier dysfunction. Colorectal protein profile analysis showed that LRP6 expression was decreased in dextran sulfate sodium (DSS)-induced colitis mice, and mice received fecal bacteria transplantation from stroke patients. Mice with intestinal hypoxia and intestinal epithelial cells cultured in hypoxia showed decreased expression of LRP6. Overexpression of LPR6 or its N-terminus rescued the Wnt/β-catenin signaling pathway which was inhibited by hypoxia and endoplasmic reticulum stress. In mice overexpressing of LRP6, the expression of β-catenin and DKK1 increased, Bcl2 decreased, and Bax increased. Mice with LRP6 knockout showed an opposite trend, and the expression of Claudin2, Occludin and ZO-1 decreased. Two drugs, curcumin and auranofin could alleviate intestinal barrier damage in DSS-induced colitis mice by targeting LRP-6. Therefore, gut microbiota dysbiosis and hypoxia can inhibit the LRP6 and Wnt/β-catenin pathway, and drugs targeting LRP6 can protect the intestinal barrier.

Keywords: gut microbiota, low-density lipoprotein receptor-related protein 6, endoplasmic-reticulum stress, beta-catenin, hypoxia, tight junction

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APA
Liu, Z., Li, C., Liu, M., Song, Z., Moyer, M.P., Su, D. (2022). The Low-density Lipoprotein Receptor-related Protein 6 Pathway in the Treatment of Intestinal Barrier Dysfunction Induced by Hypoxia and Intestinal Microbiota through the Wnt/β-catenin Pathway. International Journal of Biological Sciences, 18(11), 4469-4481. https://doi.org/10.7150/ijbs.72283.

ACS
Liu, Z.; Li, C.; Liu, M.; Song, Z.; Moyer, M.P.; Su, D. The Low-density Lipoprotein Receptor-related Protein 6 Pathway in the Treatment of Intestinal Barrier Dysfunction Induced by Hypoxia and Intestinal Microbiota through the Wnt/β-catenin Pathway. Int. J. Biol. Sci. 2022, 18 (11), 4469-4481. DOI: 10.7150/ijbs.72283.

NLM
Liu Z, Li C, Liu M, Song Z, Moyer MP, Su D. The Low-density Lipoprotein Receptor-related Protein 6 Pathway in the Treatment of Intestinal Barrier Dysfunction Induced by Hypoxia and Intestinal Microbiota through the Wnt/β-catenin Pathway. Int J Biol Sci 2022; 18(11):4469-4481. doi:10.7150/ijbs.72283. https://www.ijbs.com/v18p4469.htm

CSE
Liu Z, Li C, Liu M, Song Z, Moyer MP, Su D. 2022. The Low-density Lipoprotein Receptor-related Protein 6 Pathway in the Treatment of Intestinal Barrier Dysfunction Induced by Hypoxia and Intestinal Microbiota through the Wnt/β-catenin Pathway. Int J Biol Sci. 18(11):4469-4481.

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