Role of a RhoA/ROCK-Dependent Pathway on Renal Connexin43 Regulation in the Angiotensin II-Induced Renal Damage
Abstract
:1. Introduction
2. Results
2.1. Four Weeks of Treatment with AngII Causes an Increase in Blood Pressure and Decrease in Renal Function
2.2. The Suspension of AngII Infusion does not Reduce OS, Inflammation or Renal Tissue Damage in Rats Infused with AngII for 4 Weeks
2.3. The Increase in Cx43 and Activation of RhoA/ROCK Become Independent of the Stimulus after 4 Weeks of Treatment with AngII
2.4. Fasudil Prevents Kidney Damage, OS, Inflammation, Fibrosis, and the Increase in Protein Amount of Cx43, but does not Decrease SBP in Rats Treated with AngII
3. Discussion
4. Materials and Methods
4.1. Reagents and Antibodies
4.2. Animals
4.3. AngII Administration and Experimental Procedure
4.4. Blood Pressure Measurements
4.5. Renal Function Measurements
4.6. Thiobarbituric Acid Reactive Substances (TBARS) Measurement
4.7. Histological Damage Assessment
4.8. Tissue Processing and Immunohistochemical Analysis
4.9. Enzyme-linked Immunosorbent Assay (ELISA)
4.10. Western Blot Assays
4.11. Statistical Analysis
Author Contributions
Acknowledgments
Conflicts of Interest
Abbreviations
AngII | Angiotensin II |
CKD | Chronic kidney disease |
Col III | Collagen type III |
Cx GJs | Connexin gap junctions |
Cx HCs | Connexin hemichannels |
Cx43 | Connexin 43 |
ED-1 | Marker of macrophage infiltration |
GFR | Glomerular filtration rate |
IL-1β | Interleukin-1β |
MDA | Malondialdehyde |
MYPT-1 | Myosin phosphatase target subunit 1 |
NFκB | Nuclear factor kappa-light-chain-enhancer of activated B cells |
NOX | Nicotinamide adenine dinucleotide phosphate (NADPH) oxidase |
OPN | Osteopontin |
OS | Oxidative stress |
RAS | Renin angiotensin system |
Rho GTPase | Rho family of small GTPases |
ROCK | Rho kinase |
ROS | Reactive oxidative species |
SBP | Systolic blood pressure |
TBARS | Thiobarbituric reactive species |
TGF-β | Transforming growth factor beta |
TNF-α | Tumor necrosis factor-α |
UProt/UCrea | Ratio urine protein/urine creatinine |
α-SMA | Alpha-smooth muscle actin |
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Groups | Weigth (gr) | Proteinuria (mg/day) | Creatinine Clearence (ml/min) | FE Na + (%) | FE K + (%) |
---|---|---|---|---|---|
Ctrl | 482 ± 31 | 2.7 ± 1.1 *** | 1.4 ± 0.3 *** | 0.2 ± 0.0 *** | 12.0 ± 2.7 *** |
Ctrll+fasudil | 480 ± 36 | 3.6 ± 1.1 *** | 2.1± 0.1 *** | 0.1 ± 0.0 *** | 12.5 ± 0.3 *** |
AngII | 364 ± 42 | 214.0 ± 19.0 | 0.7 ± 0.0 | 2.2 ± 0.4 | 162.0 ± 23.0 |
AngII+fasudil | 368 ± 17 | 19 ± 7.2 *** | 1.9 ± 0.2 *** | 0.5 ± 0.1 *** | 30 ± 7.2 *** |
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Gómez, G.I.; Velarde, V.; Sáez, J.C. Role of a RhoA/ROCK-Dependent Pathway on Renal Connexin43 Regulation in the Angiotensin II-Induced Renal Damage. Int. J. Mol. Sci. 2019, 20, 4408. https://doi.org/10.3390/ijms20184408
Gómez GI, Velarde V, Sáez JC. Role of a RhoA/ROCK-Dependent Pathway on Renal Connexin43 Regulation in the Angiotensin II-Induced Renal Damage. International Journal of Molecular Sciences. 2019; 20(18):4408. https://doi.org/10.3390/ijms20184408
Chicago/Turabian StyleGómez, Gonzalo I., Victoria Velarde, and Juan C. Sáez. 2019. "Role of a RhoA/ROCK-Dependent Pathway on Renal Connexin43 Regulation in the Angiotensin II-Induced Renal Damage" International Journal of Molecular Sciences 20, no. 18: 4408. https://doi.org/10.3390/ijms20184408