Assessing Kidney Injury Induced by Mercuric Chloride in Guinea Pigs with In Vivo and In Vitro Experiments
Abstract
:1. Introduction
2. Results and Discussion
2.1. Dose Optimization of Mercuric Chloride in Guinea Pigs
2.2. Gene-Level Analysis
2.3. Kidney Injury Module Activation Analysis
2.4. Correlation between Guinea Pig and Rat Mercuric Chloride Exposures
2.5. KEGG Pathway Analysis
3. Materials and Methods
3.1. Experimental Design for In Vivo Studies
3.1.1. Animals
3.1.2. Preliminary Studies for Optimization of Dose and Time after Exposure
3.1.3. Studies for Measuring Changes in Gene Expression
3.2. Experimental Design for In Vitro Studies
3.2.1. Animals
3.2.2. Guinea Pig Renal Proximal Tubular Epithelial Cell Isolation and Culture
3.2.3. Preliminary Studies to Ascertain the Optimal Exposure of Toxicant
3.2.4. Exposure of Cells to Toxicant for RNA Isolation
3.3. RNA Sequencing
3.4. Analysis of RNA-seq Data
3.5. Injury Module Activation and Pathway Analysis
4. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
Disclaimer
References
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Common Differential Expression Genes (DEGs) | ||||||
---|---|---|---|---|---|---|
In vivo | In vivo | |||||
Overlap | 9 h | 33 h | ||||
LD | HD | LD | HD | |||
9 h | LD | 4272 | 3814 | 452 | 3296 | |
HD | 5665 | 542 | 4211 | |||
33 h | LD | 836 | 784 | |||
HD | 8264 | |||||
In vitro | In vitro | |||||
Overlap | 12 h | 24 h | ||||
LD | HD | LD | HD | |||
12 h | LD | 4377 | 3698 | 2240 | 2346 | |
HD | 7540 | 2588 | 3246 | |||
24 h | LD | 3174 | 2397 | |||
HD | 4286 | |||||
In vivo | In vitro | |||||
Overlap | 12 h | 24 h | ||||
LD | HD | LD | HD | |||
9 h | LD | 1808 | 2650 | 1275 | 1534 | |
HD | 2250 | 3441 | 1676 | 2041 | ||
33 h | LD | 332 | 466 | 248 | 289 | |
HD | 2877 | 4679 | 2171 | 2825 |
KEGG Pathway | Benjamini p-Value |
---|---|
Cell cycle | 3.8 × 10−11 |
ECM-receptor interaction | 1.2 × 10−8 |
DNA replication | 7.6 × 10−8 |
Metabolic pathways | 1.8 × 10−6 |
Focal adhesion | 2.2 × 10−6 |
PI3K-Akt signaling pathway | 2.4 × 10−6 |
Fluid shear stress and atherosclerosis | 2.4 × 10−6 |
p53 signaling pathway | 5.7 × 10−5 |
Glutathione metabolism | 8.9 × 10−5 |
Regulation of actin cytoskeleton | 3.9 × 10−3 |
Drug metabolism—other enzymes | 8.2 × 10−3 |
TNF signaling pathway | 8.2 × 10−3 |
Glycine, serine, and threonine metabolism | 1.6 × 10−2 |
Peroxisome | 1.7 × 10−2 |
Chemical carcinogenesis—reactive oxygen species | 3.2 × 10−2 |
Gene (Down) | log2 (FC) | Gene (Up) | log2 (FC) |
---|---|---|---|
Slc7a13 | −1.98 | Gsta2 | 7.07 |
Cbr1 | −1.73 | Gsta5 | 7.07 |
LOC100360601 | −1.73 | Mt2A | 6.47 |
LOC102556347 | −1.73 | Mt1m | 6.47 |
Ppp1r3c | −1.42 | Gsto1 | 3.04 |
Cltrn | −1.41 | Mt1 | 2.69 |
Smoc1 | −1.17 | Uchl1 | 2.51 |
Cd200 | −1.15 | Gstp1 | 1.65 |
Col11a1 | −1.04 | Rrm2 | 1.61 |
Bend5 | −1.00 | Aldh1a7 | 1.57 |
Kidney Injury Modules | In Vivo | In Vitro | ||||||
---|---|---|---|---|---|---|---|---|
9 h | 33 h | 12 h | 24 h | |||||
LD | HD | LD | HD | LD | HD | LD | HD | |
Dilatation | 1.51 | 2.72 | 5.65 | 10.45 | 0.51 | 2.94 | 0.63 | 2.59 |
Hyaline cast | 2.38 | 3.54 | 4.29 | 9.64 | 0.32 | 1.73 | 0.41 | 1.20 |
Degeneration | 2.55 | 3.09 | 4.74 | 7.58 | 2.74 | 1.10 | 0.31 | 0.96 |
Necrosis | 5.05 | 6.10 | 3.45 | 6.70 | 1.57 | 2.74 | 1.77 | 1.72 |
Fibrogenesis | 2.07 | 2.79 | 2.18 | 3.67 | 3.03 | 5.11 | 1.03 | 2.34 |
Intracytoplasmic inclusion body | 0.68 | 1.43 | 0.17 | 3.50 | 1.51 | 4.88 | 0.39 | 0.85 |
Hypertrophy | 0.32 | −0.43 | −0.04 | 1.50 | −0.21 | 0.80 | 0.65 | −0.52 |
Cellular infiltration | −1.63 | −1.04 | 2.15 | 0.04 | 4.06 | 2.05 | 1.35 | 0.82 |
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Goel, H.; Printz, R.L.; Shiota, C.; Estes, S.K.; Pannala, V.; AbdulHameed, M.D.M.; Shiota, M.; Wallqvist, A. Assessing Kidney Injury Induced by Mercuric Chloride in Guinea Pigs with In Vivo and In Vitro Experiments. Int. J. Mol. Sci. 2023, 24, 7434. https://doi.org/10.3390/ijms24087434
Goel H, Printz RL, Shiota C, Estes SK, Pannala V, AbdulHameed MDM, Shiota M, Wallqvist A. Assessing Kidney Injury Induced by Mercuric Chloride in Guinea Pigs with In Vivo and In Vitro Experiments. International Journal of Molecular Sciences. 2023; 24(8):7434. https://doi.org/10.3390/ijms24087434
Chicago/Turabian StyleGoel, Himanshu, Richard L. Printz, Chiyo Shiota, Shanea K. Estes, Venkat Pannala, Mohamed Diwan M. AbdulHameed, Masakazu Shiota, and Anders Wallqvist. 2023. "Assessing Kidney Injury Induced by Mercuric Chloride in Guinea Pigs with In Vivo and In Vitro Experiments" International Journal of Molecular Sciences 24, no. 8: 7434. https://doi.org/10.3390/ijms24087434