Persistent Lipid Accumulation Leads to Persistent Exacerbation of Endoplasmic Reticulum Stress and Inflammation in Progressive NASH via the IRE1α/TRAF2 Complex
Abstract
:1. Introduction
2. Results
2.1. Continuous Lipid Accumulation Dysregulated the Concentration of Blood Lipids Related Indicators
2.2. Persistent Lipid Accumulation Caused Hepatocyte Structure Impairment, Collagen Fibers, and Lipid Droplets Accumulation
2.3. Genes Expression Analysis
2.4. Differential Expressed Genes (DEGs) Analysis, Protein–Protein Interaction (PPI) Network Construction, and Core Genes Screening
2.5. Function Analysis of Differential Expressed Genes
2.6. Unremitting Lipid Accumulation Destroys the ER Structure and Increases Numbers of Lipid Droplets
2.7. Constant Lipid Accumulation Increased the Levels of TNF-α, IL-1β, and IL-6
2.8. Sustaining Lipid Accumulation Activated the IRE1α/TRAF2 Complex
2.9. Continuous Lipid Accumulation Activated the IKK/IκB/NF-κB Signaling Pathway
2.10. Persistent Lipid Accumulation Activated the ASK1/JNK1 Signaling Pathway
3. Discussion
4. Materials and Methods
4.1. Animals and High Fat Diet
4.2. NASH Model and Sample Collection
4.3. Blood Lipids Related Indicators Analysis
4.4. Histological Staining
4.5. MRNA Sequencing
4.6. PPI Network Construction and Gene Screening
4.7. Transmission Electron Microscopy
4.8. Enzyme-Linked Immunosorbent Assay
4.9. Immunofluorescence Staining
4.10. Quantitative Real-Time Polymerase Chain Reaction
4.11. Western Blotting
4.12. Statistical Analysis
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
Sample Availability
References
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Gene Name | Forward/Reverse | Primer Sequences (5′-3′) |
---|---|---|
GAPDH | Forward | ACG GCA AGT TCA ACG GCA CAG |
Reverse | GAA GAC GCC AGT AGA CTC CAC GAC | |
IRE1α | Forward | CCT GGC ACT GAA GGT TGG AT |
Reverse | GAG TGG AAG CAG TCA AGG CT | |
TRAF2 | Forward | AGC CTT CTT CAC AAG CAG ATA TG |
Reverse | GGT CCA GCA ACA TCA AAG TCA | |
IKK-β | Forward | TGA ACG AGG ATG AGA AGA CTG T |
Reverse | TGG AAG GCT GGG ACA TTA GAT | |
IκB-α | Forward | GTC TCG CTC CTG TTG AAG TG |
Reverse | GTG TCA TAG CTC TCC TCA TCC T | |
NF-κB | Forward | AGA GAA GCA CAG ATA CCA CTA AGA |
Reverse | GTT CAG CCT CAT AGA AGC CAT C | |
ASK1 | Forward | ACC TGA ACG CTC CTG GTA CA |
Reverse | TCC TCA GCC AGA AAC CGA CT | |
JNK1 | Forward | CTC TCC AGC ACC CGT ACA TC |
Reverse | CGC CAT TCT TAG TTC GCT CC |
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Lei, N.; Song, H.; Zeng, L.; Ji, S.; Meng, X.; Zhu, X.; Li, X.; Feng, Q.; Liu, J.; Mu, J. Persistent Lipid Accumulation Leads to Persistent Exacerbation of Endoplasmic Reticulum Stress and Inflammation in Progressive NASH via the IRE1α/TRAF2 Complex. Molecules 2023, 28, 3185. https://doi.org/10.3390/molecules28073185
Lei N, Song H, Zeng L, Ji S, Meng X, Zhu X, Li X, Feng Q, Liu J, Mu J. Persistent Lipid Accumulation Leads to Persistent Exacerbation of Endoplasmic Reticulum Stress and Inflammation in Progressive NASH via the IRE1α/TRAF2 Complex. Molecules. 2023; 28(7):3185. https://doi.org/10.3390/molecules28073185
Chicago/Turabian StyleLei, Na, Hongfei Song, Ling Zeng, Shaoxiu Ji, Xiangbo Meng, Xiuying Zhu, Xiuyan Li, Quansheng Feng, Jibin Liu, and Jie Mu. 2023. "Persistent Lipid Accumulation Leads to Persistent Exacerbation of Endoplasmic Reticulum Stress and Inflammation in Progressive NASH via the IRE1α/TRAF2 Complex" Molecules 28, no. 7: 3185. https://doi.org/10.3390/molecules28073185