Ipragliflozin Ameliorates Endoplasmic Reticulum Stress and Apoptosis through Preventing Ectopic Lipid Deposition in Renal Tubules
Abstract
:1. Introduction
2. Results
2.1. Effects of Ipragliflozin on Fatty Liver Shionogi ob/ob (FLS-ob/ob) Mice
2.2. Impact of Ipragliflozin on the Histological Changes in FLS-ob/ob Mice
2.3. Advanced Glycation End Product in Plasma and Kidney
2.4. Reduced Endoplasmic Reticulum Stress in FLS-ob/ob Mice Treated with Ipraglifilozin
2.5. Ipragliflozin Reduced Cellular Apoptosis in FLS-ob/ob Mice
3. Discussion
4. Materials and Methods
4.1. Animals and Experimental Designs
4.2. Histological Analysis
4.3. Quantification of AGE in the Plasma and Kidney
4.4. Apoptosis Assay in Tissues
4.5. Gene Expression Analysis
4.6. Western Blot Analysis
4.7. Statistical Analysis
Supplementary Materials
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
Abbreviations
CKD | Chronic kidney disease |
NASH | Non-alcoholic steatohepatitis |
ELD | Ectopic lipid deposition |
ER | Endoplasmic reticulum |
SGLT2 | Sodium-glucose cotransporter-2 |
FLS-ob/ob | Fatty liver Shionogi ob/ob |
BW | Body weight |
AGE | Advanced glycation end product |
GRP78 | Glucose-regulated protein-78 |
PERK | Protein kinase RNA-activated-like ER kinase |
eIF2α | Eukaryotic initiation factor 2α |
IRE1α | Inositol requiring enzyme 1α |
ATF6 | Activating transcription factor 6 |
CHOP | C/EBP homologous protein |
NFkB | Nuclear factor kappa B |
DGAT | Diacylglycerol O-acyltransferase |
ATGL | Adipose triglyceride lipase |
TUNEL | Terminal deoxynucleotidyl transferase dUTP nick end labeling |
TNF-α | Tumor necrosis factor-alfa |
PAS | Periodic acid-Schiff |
DAPI | 4′,6-diamidino-2-phenylindole |
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Parameter | Control | Ipragliflozin | p-Value |
---|---|---|---|
BW (g) | 51.6 ± 2.6 | 53.4 ± 1.6 | 0.573 |
Kidney weight/BW | 1.3 ± 0.2 | 1.3 ± 0.1 | 0.816 |
Urine volume (mL/day) | 7.6 ± 1.9 | 3.3 ± 1.2 | 0.086 |
Blood glucose (mg/dL) | 295.7 ± 64.4 | 183.3 ± 32.2 | 0.150 |
Serum triglyceride (mg/dL) | 255.6 ± 39.2 | 154.0 ± 14.0 | 0.041 * |
Creatinine clearance (mL/min/kg) | 7.3 ± 1.6 | 5.7 ± 2.2 | 0.568 |
Urinary protein (g/g/Cr) | 13.2 ± 1.3 | 10.2 ± 2.2 | 0.256 |
Gene Product | Forward Primer (5′-3′) | Reverse Primer (5′-3′) |
---|---|---|
Grp78 | GAG GCG TAT TTG GGA AAG AAG G | GCT GCT GTA GGC TCA TTG ATG |
Perk | TAT GCT ACG CAC ACG GGA CAA | ACT CGT TCC ATC TGG GTG CTG |
Eif2a | GCA CTA CAT TGC AAC AAA TGG | CAA ACA CAG GAT CAC ACT TCA G |
Chop | AGC TGG AAG CCT GGT ATG AG | AGC TAG GGA TGC AGG GTC AA |
Ire1a | AAG GCT GGA TGG CAC CAG AG | ATG TTG GCC TGT CGG TAG AGA |
Atf6 | TCG CCT TTT AGT CCG GTT CTT | GGC TCC ATA GGT CTG ACT CC |
Nfkb1 | ATTCCGCTATGTGTGTGAAGG | GTGACCAACTGAACGATAACC |
Actb | GCA TCC TCA CCC TGA AGT A | TGT GGT GCC AGA TTT TCT CC |
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Hosokawa, K.; Takata, T.; Sugihara, T.; Matono, T.; Koda, M.; Kanda, T.; Taniguchi, S.; Ida, A.; Mae, Y.; Yamamoto, M.; et al. Ipragliflozin Ameliorates Endoplasmic Reticulum Stress and Apoptosis through Preventing Ectopic Lipid Deposition in Renal Tubules. Int. J. Mol. Sci. 2020, 21, 190. https://doi.org/10.3390/ijms21010190
Hosokawa K, Takata T, Sugihara T, Matono T, Koda M, Kanda T, Taniguchi S, Ida A, Mae Y, Yamamoto M, et al. Ipragliflozin Ameliorates Endoplasmic Reticulum Stress and Apoptosis through Preventing Ectopic Lipid Deposition in Renal Tubules. International Journal of Molecular Sciences. 2020; 21(1):190. https://doi.org/10.3390/ijms21010190
Chicago/Turabian StyleHosokawa, Kohshiro, Tomoaki Takata, Takaaki Sugihara, Tomomitsu Matono, Masahiko Koda, Tsutomu Kanda, Sosuke Taniguchi, Ayami Ida, Yukari Mae, Marie Yamamoto, and et al. 2020. "Ipragliflozin Ameliorates Endoplasmic Reticulum Stress and Apoptosis through Preventing Ectopic Lipid Deposition in Renal Tubules" International Journal of Molecular Sciences 21, no. 1: 190. https://doi.org/10.3390/ijms21010190