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Inhibition of YAP activation attenuates renal injury and fibrosis in angiotensin II hypertensive mice
- Source :
- Canadian Journal of Physiology and Pharmacology. 99:1000-1006
- Publication Year :
- 2021
- Publisher :
- Canadian Science Publishing, 2021.
-
Abstract
- The Hippo/YAP (yes-associated protein) pathway is an important signaling pathway to control organ development and tissue homeostasis. YAP is a downstream effector of the Hippo pathway and a critical mediator of mechanic stress. Hypertensive nephropathy is characterized with glomerular sclerosis stiffness and renal fibrosis. The present study investigated the role of YAP pathway in angiotensin (Ang) II hypertensive renal injury by using YAP activation inhibitor verteporfin. Ang II increased the protein expression of YAP in renal nucleus fraction, decreased phospho-YAP, and phospho-LATS1/2 (large tumor suppressors 1 and 2) expressions in renal cytoplasmic fraction, suggesting Ang II activation of renal YAP. Ang II significantly increased systolic blood pressure (SBP), proteinuria, glomerular sclerosis, and fibrosis; treatment with verteporfin attenuated Ang II–induced proteinuria and renal injury with a mild reduction in SBP. Moreover, Ang II increased the protein expressions of inflammatory factors including tumor necrosis factor α, interleukin 1β, and monocyte chemoattractant protein-1, and profibrotic factors including transforming growth factor β, phospho-Smad3 and fibronectin. Verteporfin reversed abovementioned Ang II–induced molecule expressions. Our results for the first time demonstrate that the activation of the YAP pathway promotes hypertensive renal inflammation and fibrosis, which may promote hypertensive renal injury. YAP may be a new target for prevention and treatment of hypertensive renal diseases.
- Subjects :
- Male
0301 basic medicine
Hypertension, Renal
Physiology
Blood Pressure
Inflammation
Protein Serine-Threonine Kinases
030204 cardiovascular system & hematology
urologic and male genital diseases
Mice
03 medical and health sciences
0302 clinical medicine
Transforming Growth Factor beta
Fibrosis
Physiology (medical)
medicine
Renal fibrosis
Animals
Vasoconstrictor Agents
Chemokine CCL2
Tissue homeostasis
Pharmacology
Hippo signaling pathway
Nephritis
Photosensitizing Agents
Effector
business.industry
Angiotensin II
Verteporfin
YAP-Signaling Proteins
General Medicine
Acute Kidney Injury
medicine.disease
Mice, Inbred C57BL
030104 developmental biology
Hypertension
Cancer research
medicine.symptom
Signal transduction
business
Signal Transduction
Subjects
Details
- ISSN :
- 12057541 and 00084212
- Volume :
- 99
- Database :
- OpenAIRE
- Journal :
- Canadian Journal of Physiology and Pharmacology
- Accession number :
- edsair.doi.dedup.....aee6b9c1146f4b10ea464f1cbaa9fa4f