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Hepatic Sinusoid Capillarizate via IGTAV/FAK Pathway Under High Glucose

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A Correction to this article was published on 30 November 2023

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Abstract

The incidence of diabetic patients with non-alcoholic fatty liver disease (NAFLD) is continuously increasing worldwide. However, the specific mechanisms of NAFLD patients with diabetes are still not clear. Recent studies have indicated that integrins play an important role in NAFLD. In this study, we considered the relationship between integrin αv (IGTAV)/FAK pathway and sinusoidal capillarization. We investigated the difference between the expression of IGTAV, laminin (LN), focal adhesion kinase (FAK), and phosphor-FAK protein in human liver sinusoidal endothelial cells (HLSECs) to explore the specific mechanisms of the diseases of NAFLD with diabetes under high glucose. We cultured and identified the HLSECs and constructed the recombinant lentivirus vector with IGTAV shRNA by quantitative real-time PCR (qRT-PCR) to silence the IGTAV gene. Cells were divided into groups of 25 mmol/L glucose and 25 mmol/L mannitol. We measured the protein levels of IGTAV, LN, FAK, and phosphor-FAK by western blot at 2 h, 6 h, and 12 h before and after IGTAV gene silencing. The lentivirus vector was successfully constructed with IGTAV shRNA. The HLSECs under high glucose were observed by scanning electron microscope. SPSS19.0 was used for statistical analysis. High glucose significantly increased the expression of IGTAV, LN, and phosphor-FAK protein in HLSECs; the shRNA IGTAV could effectively inhibit the expression of phosphor-FAK and LN at 2 h and 6 h. Inhibition of the phosphor-FAK could effectively decrease the expression of LN in HLSECs at 2 h and 6 h under high glucose. Inhibition of IGTAV gene of HLSECs under high glucose could improve hepatic sinus capillarization. Inhibition of IGTAV and phosphor-FAK decreased the expression of LN. High glucose led to hepatic sinus capillarization via IGTAV/ FAK pathway.

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Abbreviations

NAFLD:

non-alcoholic fatty liver disease

LSECs:

liver sinusoidal endothelial cells

ECM:

extracellular matrix

LN:

laminin

GPI:

glycosylphosphatidylinositol

FAK:

focal adhesion kinase

IGTAV:

integrin αv

DMEM:

Dulbecco’s Modified Eagle’s Medium

FBS:

fetal bovine serum

HLSECs:

human liver sinusoidal endothelial cells

shRNA:

short hairpin RNA

EDTA:

ethylenediaminetetraacetic acid

cDNA:

complementary DNA

qRT-PCR:

quantitative real-time polymerase chain reaction

2-DDCT:

delta-delta CT

SDS-PAGE:

sodium dodecyl sulfate-polyacrylamide gel electrophoresis

RNAi:

RNA interference

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Acknowledgements

Addressed all correspondence and requests for reprints to: Jing Liu, PhD, Department of Endocrinology, Gansu Provincial Hospital, Lanzhou City, Gansu province, China, 730000. Email: yongshen986@163.com.

Funding

This work has been supported by the National Natural Science Foundation of China, (81360131, 81560146, 81660148).

Author information

Authors and Affiliations

  1. The First Clinical College of Lanzhou University, Lanzhou, 730000, Gansu province, China

    Jia Liu & Jing Liu

  2. Department of Endocrinology, Gansu Provincial Hospital, Donggang west Road 160, Lanzhou city, 730000, Gansu province, China

    Jia Liu, Jinxing Quan, Limin Tian, Qi Zhang, Juxiang Liu & Jing Liu

  3. Department of General Practice, The First Hospital of Lanzhou University, Lanzhou city, 730000, Gansu province, China

    Hengjiang Gong

  4. Department of Intensive Care, Gansu Provincial Hospital, Lanzhou city, 730000, Gansu province, China

    Dongquan Zhang

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  1. Jia Liu
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 Jia Liu and Hengjiang Gong contributed equally.

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Correspondence to Jing Liu.

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Liu, J., Gong, H., Quan, J. et al. Hepatic Sinusoid Capillarizate via IGTAV/FAK Pathway Under High Glucose. Appl Biochem Biotechnol 196, 1241–1254 (2024). https://doi.org/10.1007/s12010-023-04605-8

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