Affiliation:
1. Division of Cell Regeneration and Transplantation Department of Functional Morphology Nihon University School of Medicine Tokyo Japan
2. Division of Nephrology, Hypertension, and Endocrinology Department of Medicine Nihon University School of Medicine Tokyo Japan
3. Research Center Nihon University Tokyo Japan
Abstract
Background
We previously reported that vascular smooth muscle cells (
VSMC
s) from spontaneously hypertensive rats (
SHR
s) show the increased expression of complement 3 (C3) and the synthetic phenotype. We targeted the
SHR
C3 gene (C3 knockout [C3
KO] SHRs
) by the zinc finger gene editing method. In the current study, we investigated the mechanisms underlying the increased expression of C3 and the role of endogenous C3 in the synthetic phenotype of
SHR VSMC
s in comparison to cells from Wistar‐Kyoto (
WKY)
rats and C3
KO SHR
s.
Methods and Results
Nonmuscle myosin heavy chain staining of aortas from
SHR
s at 1 day after birth was stronger in comparison to
WKY
rats and C3
KO SHR
s.
DNA
synthesis in
VSMC
s from
SHR
s was significantly higher in comparison to
WKY
rats and C3
KO SHR
s. Immunohistochemical staining of renin and liver X receptor α in
VSMC
s from
SHR
s was stronger in comparison to
WKY
rats and C3
KO SHR
s. The expression of renin, Krüppel‐like factor 5, and liver X receptor α proteins in
VSMC
s from
SHR
s was significantly higher in comparison to
WKY
rats and C3
KO SHR
s. The expression of synthetic phenotype markers osteopontin, matrix gla, and
l
‐caldesmon, growth factors transforming growth factor‐β1 and platelet‐derived growth factor‐A, transcription factors Krüppel‐like factor 5 and liver X receptor α, and angiotensinogen
mRNA
s in
VSMC
s from
SHR
s was significantly higher in comparison to
WKY
rats and C3
KO SHR
s. The expression of miR‐145
mRNA
in
VSMC
s from
SHR
s was suppressed in comparison to cells from
WKY
rats. miR‐145 inhibitor significantly increased the expression of C3 in
VSMC
s from
WKY
rats, but not in cells from
SHR
s.
Conclusions
These findings indicate that the increased C3 with the suppression of miR‐145 induces the synthetic phenotype through Krüppel‐like factor 5 and the activation of the renin‐angiotensin system through liver X receptor α in
VSMC
s from
SHR
s.
Publisher
Ovid Technologies (Wolters Kluwer Health)
Subject
Cardiology and Cardiovascular Medicine
Cited by
11 articles.
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