Transforming growth factor β1 induces mitogenesis in fetal rat brown adipocytes

Teruel, Teresa; Valverde, Ángela M.; Benito, Manuel; Lorenzo, Margarita

doi:10.1002/(sici)1097-4652(199603)166:3<577::aid-jcp12>3.0.co;2-4

Cited by 15 publications

(9 citation statements)

References 42 publications

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“…A glomerulus therefore may not provide adequate physical conditions for chondrogenic differentiation. Rather, TGF-␤, which is secreted in high amounts by our MSC in vitro (6), acts as a major signal for adipogenesis (27,28). Another factor that strongly enhances adipogenic differentiation of MSC in vitro is basic fibroblast growth factor (29), which is released within the glomerulus during early anti-Thy1.1 nephritis (30).…”

Section: Discussionmentioning

confidence: 99%

Mesenchymal Stem Cells Prevent Progressive Experimental Renal Failure but Maldifferentiate into Glomerular Adipocytes

Kunter

Rong

Boor

et al. 2007

Journal of the American Society of Nephrology

258

163

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Glomerulonephritis (GN) isM esenchymal stem cells (MSC) hold special promise for renal repair, because nephrons are largely of mesenchymal origin (1). The potential of MSC for renal repair has been shown in rodent models of acute renal failure (ARF), where the course of glycerol, cisplatin, or ischemia-reperfusion induced ARF was improved by MSC injection shortly after disease induction (2-5). In addition, we recently reported that injection of rat MSC into a renal artery can accelerate recovery from mesangiolytic damage and prevent transient ARF in rat anti-Thy1.1 glomerulonephritis (GN) (6). AntiThy1.1 nephritis is a model of acute mesangioproliferative glomerulonephritis and is characterized by initial mesangiolysis followed within a few days by glomerular repair via endothelial and mesangial cell proliferation and accumulation of mesangial matrix. We have also provided evidence that MSC likely exerted these effects in glomeruli by paracrine effects, such as the release of high amounts of vascular endothelial growth factor (VEGF) and TGF-␤1 rather than by differentiation into resident glomerular cell types or monocytes/macrophages (6).In this study, we investigated the long-term effects of MSC administration in early anti-Thy1.1 nephritis. Normally, antiThy1.1 nephritis in rats follows a self-limited course, and spontaneous restitution of the glomerular architecture can be observed within approximately 4 wk. For enhancement of the relevance of the model for progressive renal disease in humans, the model in this study was aggravated and transformed into a course of progressive renal failure by previous uninephrectomy of the rats (7,8). Materials and MethodsRats were housed under standard conditions in a light-, temperature-, and humidity-controlled environment with free access to tap water and standard rat diet. All animal protocols were approved by the local government authorities. Harvest and Culture of MSCInbred male Lewis rats that weighed 180 to 210 g (Harlan, Horst, Netherlands) served as bone marrow donors; MSC were prepared as described previously (6). Cells were seeded onto six-well plates (nine

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Section: Discussionmentioning

confidence: 99%

Mesenchymal Stem Cells Prevent Progressive Experimental Renal Failure but Maldifferentiate into Glomerular Adipocytes

Kunter

Rong

Boor

et al. 2007

Journal of the American Society of Nephrology

258

163

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“…TGF-␤ upregulates G6PD expression and increases levels of NOX4-derived ROS (45), which in turn stimulate G6PD activity in a variety of cell types, including erythrocytes, hepatocytes, and smooth muscle myocytes. We found that TGF-␤ receptor blockade significantly reduced CD133 ϩ cell numbers under normoxia but not hypoxia.…”

Section: Pluripotent Cd133mentioning

confidence: 99%

“…For example, mobilization of endothelial progenitor cells is dependent on NOX2-derived ROS (9,33,37). In addition, TGF-␤ upregulates glucose-6-phosphate dehydrogenase (G6PD) expression in fetal brown adipocytes and increases levels of NOX4-derived ROS (45). Because production of superoxide anion from NOX is dependent on G6PD-derived NADPH (18,20), we hypothesized that increases in G6PD-dependent NA-DPH redox and NOX-derived ROS act in concert to mediate hypoxia-induced CD133…”

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confidence: 99%

Glucose-6-phosphate dehydrogenase plays a critical role in hypoxia-induced CD133⁺progenitor cells self-renewal and stimulates their accumulation in the lungs of pulmonary hypertensive rats

Chettimada

Joshi

Kheirallah

et al. 2014

American Journal of Physiology-Lung Cellular and Molecular Phys

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Chettimada S, Joshi SR, Alzoubi A, Gebb SA, McMurtry IF, Gupte R, Gupte SA. Glucose-6-phosphate dehydrogenase plays a critical role in hypoxia-induced CD133 ϩ progenitor cells self-renewal and stimulates their accumulation in the lungs of pulmonary hypertensive rats. Am J Physiol Lung Cell Mol Physiol 307: L545-L556, 2014. First published July 25, 2014 doi:10.1152/ajplung.00303.2013.-Although hypoxia is detrimental to most cell types, it aids survival of progenitor cells and is associated with diseases like cancer and pulmonary hypertension in humans. Therefore, understanding the underlying mechanisms that promote survival of progenitor cells in hypoxia and then developing novel therapies to stop their growth in hypoxiaassociated human diseases is important. Here we demonstrate that the proliferation and growth of human CD133 ϩ progenitor cells, which contribute to tumorigenesis and the development of pulmonary hypertension, are increased when cultured under hypoxic conditions. Furthermore, glucose-6-phosphate dehydrogenase (G6PD) activity was increased threefold in hypoxic CD133 ϩ cells. The increased G6PD activity was required for CD133 ϩ cell proliferation, and their growth was arrested by G6PD inhibition or knockdown. G6PD activity upregulated expression of HIF1␣, cyclin A, and phospho-histone H3, thereby promoting CD133 ϩ cell dedifferentiation and self-renewal and altering cell cycle regulation. When CD133 ϩ cells were cocultured across a porous membrane from pulmonary artery smooth muscle cells (PASMCs), G6PD-dependent H 2O2 production and release by PASMCs recruited CD133 ϩ cells to the membrane, where they attached and expressed smooth muscle markers (␣-actin and SM22␣). Inhibition of G6PD reduced smooth muscle marker expression in CD133 ϩ cells under normoxia but not hypoxia. In vivo, CD133 ϩ cells colocalized with G6PD ϩ cells in the perivascular region of lungs from rats with hypoxia-induced pulmonary hypertension. Finally, inhibition of G6PD by dehydroepiandrosterone in pulmonary arterial hypertensive rats nearly abolished CD133 ϩ cell accumulation around pulmonary arteries and the formation of occlusive lesions. These observations suggest G6PD plays a key role in increasing hypoxia-induced CD133 ϩ cell survival in hypertensive lungs that differentiate to smooth muscle cells and contribute to pulmonary arterial remodeling during development of pulmonary hypertension.pentose phosphate pathway; pulmonary hypertension; Notch; HIF; cyclin A; phospho-histone H3; cell cycle; dedifferentiation; phenotype; pulmonary artery smooth muscle cells MOLECULAR OXYGEN IS ESSENTIAL for most life on Earth, functioning as the final electron acceptor during the oxidation of glucose to produce energy in the form of ATP. Ironically, hypoxia promotes the survival and expansion capacity of embryonic stem cells, cancer stem cells (16,40), and neuronal crest stem cells (30, 44), as well as the differentiation potential of bone marrow-derived CD133 ϩ progenitor cells (33, 40). CD133 ϩ progenitor cells are capable of different...

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“…Mitogenic activity of recombinant rat FGF-16 for primary rat embryonic brown adipocytes cultured in a serum-free medium was determined essentially according to the method of Teruel et al (20). Primary rat embryonic brown adipocytes were plated onto 24-well plates (2 ϫ 10 4 cells/well) and cultured in modified Eagle's medium with 10% fetal calf serum.…”

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confidence: 99%

Fibroblast Growth Factor-16 Is a Growth Factor for Embryonic Brown Adipocytes

Konishi

Mikami

Yamasaki

et al. 2000

Journal of Biological Chemistry

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In rat embryos, fibroblast growth factor (FGF)-16 is predominantly expressed in brown adipose tissue. To elucidate the role of FGF-16, we examined the expression of FGF-16 mRNA in rat embryonic brown adipose tissue at different developmental stages by Northern blotting analysis and in situ hybridization. FGF-16 mRNA was expressed abundantly in brown adipose tissue during embryonic day 17.5, embryonic days 17.5-19.5, and thereafter at lower levels into the neonatal period. The expression profile of FGF-16 mRNA well corresponds to the proliferative profile of embryonic brown adipose tissue reported. We also examined the mitogenic activity of recombinant rat FGF-16 for primary brown adipocytes prepared from rat embryonic brown adipose tissue. FGF-16 showed significant mitogenic activity for primary brown adipocytes. The mitogenic activity was found to be exerted by binding and activating FGF receptor-4 in the brown adipose tissue. As a great induction of proliferation of rat brown adipose tissue during cold acclimation was reported, we also examined the expression of FGF-16 mRNA in the brown adipose tissue during cold acclimation by Northern blotting analysis. The expression of FGF-16 mRNA was not increased, but rather decreased. The expression profile of FGF-16 mRNA and the mitogenic activity of FGF-16 reported here indicate that FGF-16 is a unique growth factor involved in proliferation of embryonic brown adipose tissue.Adipose tissues serve an important function in the energy economy of vertebrate organisms by providing a massive energy reserve that can be mobilized upon demand. There are two types of adipose tissues, white and brown. Their physiological roles are quite different. White adipose tissue stores energy, whereas brown adipose tissue dissipates energy. Brown adipose tissue is a specialized tissue of mammals responsible for facultative thermogenesis. Its physiological significance has been recognized in newborns when the decrease in environmental temperature at birth requires an adaptive increase in heat production (1). Brown adipose tissue is also speculated to normally function to prevent obesity. Indeed, transgenic mice with primary deficiency of brown adipose tissue have obesity, which develops in the absence of hyperphagia. As obesity progresses, transgenic animals develop hyperphagia (2). These results support a critical role for brown adipose tissue in the nutritional homeostasis of mice.The prototypic fibroblast growth factors (FGFs), 1 FGF-1 (acidic FGF) and FGF-2 (basic FGF), were originally isolated from the brain and pituitary as mitogens for fibroblasts (3, 4). The FGF family now consists of 19 members, FGF-1 to FGF-19 (5, 6). FGFs are widely expressed in developing and adult tissues and appear to have important roles with multiple biological activities, including angiogenesis, mitogenesis, cellular differentiation, and repair of tissue injury (3,4,7,8). In rat embryos, FGF-16 mRNA was predominantly expressed in brown adipose tissue, indicating that FGF-16 plays a unique role in embryonic ...

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Transforming growth factor β1 induces mitogenesis in fetal rat brown adipocytes

Cited by 15 publications

References 42 publications

Mesenchymal Stem Cells Prevent Progressive Experimental Renal Failure but Maldifferentiate into Glomerular Adipocytes

Mesenchymal Stem Cells Prevent Progressive Experimental Renal Failure but Maldifferentiate into Glomerular Adipocytes

Glucose-6-phosphate dehydrogenase plays a critical role in hypoxia-induced CD133⁺progenitor cells self-renewal and stimulates their accumulation in the lungs of pulmonary hypertensive rats

Fibroblast Growth Factor-16 Is a Growth Factor for Embryonic Brown Adipocytes

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Transforming growth factor β1 induces mitogenesis in fetal rat brown adipocytes

Cited by 15 publications

References 42 publications

Mesenchymal Stem Cells Prevent Progressive Experimental Renal Failure but Maldifferentiate into Glomerular Adipocytes

Mesenchymal Stem Cells Prevent Progressive Experimental Renal Failure but Maldifferentiate into Glomerular Adipocytes

Glucose-6-phosphate dehydrogenase plays a critical role in hypoxia-induced CD133+progenitor cells self-renewal and stimulates their accumulation in the lungs of pulmonary hypertensive rats

Fibroblast Growth Factor-16 Is a Growth Factor for Embryonic Brown Adipocytes

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Glucose-6-phosphate dehydrogenase plays a critical role in hypoxia-induced CD133⁺progenitor cells self-renewal and stimulates their accumulation in the lungs of pulmonary hypertensive rats