Fibroblasts activation by embryonic signal switching: A novel mechanism of placental growth factor-induced cardiac remodeling

被引：2

作者：

Kitasato, Lisa ^{[1
]}

Yamaoka-Tojo, Minako ^{[2
]}

Suzuki, Machika ^{[1
]}

Nakahara, Shohei ^{[1
]}

Iwaya, Toshiyuki ^{[1
]}

Ogiso, Sho ^{[1
]}

Murayama, Yusuke ^{[1
]}

Hashikata, Takehiro ^{[1
]}

Misawa, Nonoka ^{[3
]}

Kawashima, Rei ^{[3
]}

Oikawa, Jun ^{[4
]}

Nakamura, Masaki ^{[3
,5
]}

Tokui, Yumi ^{[6
,7
]}

Naraba, Jun ^{[6
,7
]}

Nishii, Mototsugu ^{[8
]}

Kitasato, Hidero ^{[6
,7
,9
]}

Ako, Junya ^{[1
,9
]}

机构：

[1] Kitasato Univ, Dept Cardiovasc Med, Sch Med, 1-15-1 Kitasato, Sagamihara, Kanagawa 2520374, Japan

[2] Kitasato Univ, Sch Allied Hlth Sci, Dept Rehabil, 1-15-1 Kitasato, Sagamihara, Kanagawa 2520373, Japan

[3] Kitasato Univ, Dept Regulat Biochem, Sch Allied Hlth Sci, 1-15-1 Kitasato, Sagamihara, Kanagawa 2520373, Japan

[4] Kitasato Univ, Dept Kitasato Clin Res Ctr, Sch Med, 1-15-1 Kitasato, Sagamihara, Kanagawa 2520374, Japan

[5] Kitasato Univ, Sch Med, Dept Lab Med, 1-15-1 Kitasato, Sagamihara, Kanagawa 2288555, Japan

[6] Kitasato Univ, Dept Microbiol, Sch Allied Hlth Sci, 1-15-1 Kitasato, Sagamihara, Kanagawa 2520373, Japan

[7] Kitasato Univ, Dept Environm Microbiol, Grad Sch Med Sci, 1-15-1 Kitasato, Sagamihara, Kanagawa 2520373, Japan

[8] Yokohama City Univ, Dept Emergency Med, Sch Med, Kanazawa Ku, Yokohama, Kanagawa 2360004, Japan

[9] Shibasaburo Kitasato Mem Museum, 3199 Kitazato, Aso, Kumamoto 8692505, Japan

来源：

PLACENTA | 2024年 / 154卷

基金：

日本学术振兴会;

关键词：

Placental growth factor; Cardiac remodeling; Oxidative stress; Cardiac fibroblasts; Cardiomyocytes; NF-KAPPA-B; ANGIOTENSIN-II; ENDOTHELIAL-CELLS; OXIDATIVE STRESS; TYROSINE KINASE; PROTEIN-KINASES; HEART-FAILURE; EXPRESSION; TRANSCRIPTION; HYPERTROPHY;

D O I：

10.1016/j.placenta.2024.07.001

中图分类号：

Q [生物科学];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Introduction: Cardiac remodeling is defined as cellular interstitial changes that lead dysfunction of the heart after injury. Placental growth factor (PlGF), a member of the VEGF family, has been reported to regulate cardiac hypertrophy in hemodynamic state. We therefore analyze the function of PlGF during cardiac remodeling using cardiac cells and fibroblasts, under Angiotensin II (AngII) stimulation. Methods: PlGF overexpressed mouse embryonic fibroblasts derived from C57BL/6 mice, were made by deficient retrovirus vector, designated as C57/PlGF. Only retrovirus vector introduced C57 cells (C57/EV) were used as control. After AngII stimulation, wound scratching assay and MTT proliferation assay with or without p38 MAPK inhibitor, SB205580 were performed in retrovirally-introduced C57 cells. Reactive oxygen species (ROS) production, NF-kB activation, IL-6 and TNF- alpha production were also measured. Then we assessed AngII-induced cell proliferation of mouse cardiac fibroblasts (CFs) and rat primary cardiomyocytes incubating with C57/PlGF conditioned-medium. Results: The PlGF production in C57/PlGF were confirmed by ELISA (1093.48 +/- 3.5 pg/ml, +/- SE). AngII-induced cell migration, proliferation and H 2 O 2 production were increased in C57/PlGF compared with C57/EV. SB205580 inhibited the AngII-induced cell proliferation in C57/PlGF. In C57/PlGF cells, NF-kB activation was higher, followed by up-regulation of IL-6 and TNF- alpha production. CFs and cardiomyocytes proliferation increased when stimulated with C57/PlGF conditioned-medium. Discussion: The activation of fibroblast is stimulated by PlGF signaling via p38 MAPK/NF-kB pathway accompanied by elevation of ROS and inflammatory response. Furthermore, these signals stimulate the activation of CFs and cardiomyocytes, indicating that high circulating level of PlGF have a potential to regulate cardiac remodeling.

引用

页码：129 / 136

页数：8

共 57 条

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