Transforming growth factor-beta signaling enhances transdifferentiation of macrophages into smooth muscle-like cells.
Hemopoietic cells or bone marrow-derived cells contribute to tissue formation, possibly by transdifferentiation into smooth muscle cells (SMCs) or myofibroblasts. In this study our goal is to examine the effects of transforming growth factor-beta1 (TGF-beta1) on the transdifferentiation of the monocyte/macrophage lineage into SMC-like cells. Using rat peritoneal exudate macrophages, we investigated the expression of smooth muscle-specific differentiation markers, such as alpha-smooth muscle actin, embryonic smooth muscle myosin heavy chain, and calponin. The treatment of macrophages with TGF-beta1 enhanced the expression of SMC-specific markers at day 4; after 7 days in culture, a higher level of expression (approximately 3- to 5-fold) was detected on Western blots. In contrast, TGF-beta1 decreased the expression of CD11b, which is a macrophage marker. Furthermore, we examined the effect of the TGF-beta type 1 receptor inhibitor SB-431542 and a replication-defective adenovirus construct expressing Smad7 (Adeno-Smad7), which inhibits TGF-beta signaling by interfering with the activation of other Smad proteins. Both SB-431542 and Adeno-Smad7 suppressed the expression of SMC-specific markers. These results indicated that TGF-beta signaling is essential for the transdifferentiation of macrophages into SMC-like cells. Elucidating the mechanism by which macrophages transdifferentiate into SMC-like cells may reveal new therapeutic targets for preventing vascular diseases.
Ninomiya
Kozo
K
Division of Cardiovascular and Respiratory Medicine, Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe, Japan.
Takahashi
Akihiro
A
Fujioka
Yoshio
Y
Ishikawa
Yuichi
Y
Yokoyama
Mitsuhiro
M
D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D000954:Antigens, Surface / Q000378:metabolism; D001549:Benzamides / Q000494:pharmacology; D015415:Biomarkers; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D004149:Dioxoles / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005822:Genetic Vectors; D017737:Macrophages, Peritoneal / Q000166:cytology* / Q000378:metabolism; D008297:Male; D032389:Myocytes, Smooth Muscle / Q000166:cytology* / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects* / Q000502:physiology; D051906:Smad7 Protein / Q000235:genetics; D016212:Transforming Growth Factor beta / Q000378:metabolism* / Q000494:pharmacology*; D053773:Transforming Growth Factor beta1
C459179:4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide; D000954:Antigens, Surface; D001549:Benzamides; D015415:Biomarkers; D004149:Dioxoles; D051906:Smad7 Protein; C508962:Tgfb1 protein, rat; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1