Disruption of Smad7 promotes ANG II-mediated renal inflammation and fibrosis via Sp1-TGF-β/Smad3-NF.κB-dependent mechanisms in mice

Smad7 is an inhibitory Smad and plays a protective role in obstructive and diabetic kidney disease. However, the role and mechanisms of Smad7 in hypertensive nephropathy remains unexplored. Thus, the aim of this study was to investigate the role and regulatory mechanisms of Smad7 in ANG II-induced h...

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Bibliographic Details
Published in:PloS one 2013, Vol.8 (1), p.e53573-e53573
Main Authors: Liu, Guan-Xian, Li, You-Qi, Huang, Xiao R, Wei, Lihua, Chen, Hai-Yong, Shi, Yong-Jun, Heuchel, Rainer L, Lan, Hui Y
Format: Article
Language:English
Subjects:
Angiotensin II
Angiotensin II - metabolism
Animals
Biology
Blood pressure
Cell activation
Cell- och molekylärbiologi
Collagen
Diabetes mellitus
Endokrinologi och diabetes
Fibrosis
Gene Expression Regulation
Growth factors
Health sciences
Histology
Hospitals
Hypertension
Hypertension - metabolism
IL-1β
Infiltration
Inflammation
Inflammation - pathology
Injury prevention
Kidney - metabolism
Kidney diseases
Kidney Diseases - metabolism
Kinases
Klinisk medicin
Macrophages
Male
Medicin och hälsovetenskap
Medicine
Medicinska och farmaceutiska grundvetenskaper
Mice
Mice, Knockout
MicroRNAs - metabolism
Nephrology
Nephropathy
NF-kappa B - metabolism
NF-κB protein
Proteins
Proteinuria
Proteinuria - metabolism
Regulatory mechanisms (biology)
Renal function
Rodents
Signal Transduction
Signaling
Smad protein
Smad3 protein
Smad3 Protein - metabolism
Smad7 protein
Smad7 Protein - genetics
Sp1 protein
Sp1 Transcription Factor - metabolism
Transforming Growth Factor beta - metabolism
Transforming growth factor-b1
Tumor necrosis factor-α
Urine
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Summary:Smad7 is an inhibitory Smad and plays a protective role in obstructive and diabetic kidney disease. However, the role and mechanisms of Smad7 in hypertensive nephropathy remains unexplored. Thus, the aim of this study was to investigate the role and regulatory mechanisms of Smad7 in ANG II-induced hypertensive nephropathy. Smad7 gene knockout (KO) and wild-type (WT) mice received a subcutaneous infusion of ANG II or control saline for 4 weeks via osmotic mini-pumps. ANG II infusion produced equivalent hypertension in Smad7 KO and WT mice; however, Smad7 KO mice exhibited more severe renal functional injury as shown by increased proteinuria and reduced renal function (both p
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0053573