Pref-1, a protein containing EGF-like repeats, inhibits adipocyte differentiation

Smas, Cynthia M.; Sul, Hei Sook

doi:10.1016/0092-8674(93)90252-l

Cited by 617 publications

(612 citation statements)

References 71 publications

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“…Dlk1 is a modulator of adipogenesis. 52,53 Different isoforms of Dlk1 may have opposite roles in the control of adipogenesis; however, it is agreed that Dlk1 is elevated in the preadipocytic state. With age progression, an adi- pogenic program overcomes osteogenesis 54 (rat marrow cells) and myogenesis 55 (murine myoblasts).…”

Section: Discussionmentioning

confidence: 99%

Defective Myofibroblast Formation from Mesenchymal Stem Cells in the Aging Murine Heart

Cieslik

Trial

Entman

2011

The American Journal of Pathology

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Cardiac fibroblasts are the most prevalent cell type in the heart. These cells exert a critical role in regulating normal myocardial function and in the adverse myocardial remodeling that occurs after myocardial infarction (MI). 1 Irreversible cardiomyocyte damage owing to cessation of oxygen supply during MI leads to necrosis, which stimulates inflammatory reactions that trigger reparative pathways and activate cells to form a scar. Cytokines released by inflammatory infiltrating leukocytes promote endogenous mesenchymal stem cell (MSC) proliferation and migration toward the infarct site, followed by differentiation into fibroblasts that deposit scar-forming collagen. The fibroblasts mature into myofibroblasts, expressing scar-contracting ␣-smooth muscle actin (␣-SMA). 2 Resident fibroblasts also become activated and participate in this process. After several weeks, a mature scar is formed, and most of the myofibroblasts undergo apoptosis. [3][4][5] We have previously established in a model of mouse MI that, compared with young animals, aged mice demonstrate greater infarct expansion and less effective myocardial repair. 6 Defective scar formation arises from a decreased number of myofibroblasts and diminished collagen deposition in the infarct, which results in a structurally unstable scar formed by loose connective tissue. 7 Evidence indicates that multipotent cells can be generated in vitro from several adult organs including the heart. 8 Tissue-resident progenitor cells of mesenchymal origin can differentiate into myogenic, adipocytic, chondrocytic, osteoblastic, and fibroblastic lineages. 9 -11 The potential of those stem cells to differentiate decreases

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Section: Discussionmentioning

confidence: 99%

Defective Myofibroblast Formation from Mesenchymal Stem Cells in the Aging Murine Heart

Cieslik

Trial

Entman

2011

The American Journal of Pathology

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“…In preadipocyte cell lines different splice variants of Dlk1 have opposing effects on differentiation. 47,48 Dlk1 inhibits stem cell factor-induced colony formation in murine hematopoietic progenitors in a HES-independent way. 49 However there are also indications that Dlk1 is a valid partner of the Delta-Notch pathway.…”

Section: Discussionmentioning

confidence: 99%

High delta‐like 1 expression in a subset of neuroblastoma cell lines corresponds to a differentiated chromaffin cell type

Limpt

Chan

Sluis

et al. 2003

Intl Journal of Cancer

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“…Mouse Dlk1 is a protein of 385 amino acids that consists a signal peptide (amino acids 8-17), 6 EGFlike repeats (amino acids 26-246), a juxtamembrane domain which contains a protease cleavage site (amino acids 282-303), a transmembrane domain (amino acids 300-330), and a cytoplasmic tail (amino acids 331-385) [4,8] (Figure 5). Expression vectors containing either wild type Dlk1 or different truncated Dlk1 mutants were transfected into GH3 cells to determine which portion of Dlk1 is required to regulate the activity of -500GHp-luc.…”

Section: Dlk1-mediated Gh Promoter Repression Is Independent Of Its Ementioning

confidence: 99%

“…Treatment of the 3T3-L1 preadipocyte cell line with GH prevents these cells from differentiating to adipocytes, suggesting that blocking preadipocyte differentiation is one mechanism whereby GH can regulate body fat homeostasis. The ability of GH to block preadipocyte differentiation has been attributed to its ability to increase expression of Delta-like protein 1 (Dlk1) [2,3], a known inhibitor of adipogenesis [4]. Dlk1, also known as pref-1 [4], pG2 [5] and zona glomerulosa specific mRNA [6], contains 6 EGF-like repeat domains in the extracellular domain, a transmembrane domain and a short cytoplasmic tail.…”

Section: Introductionmentioning

confidence: 99%

“…The ability of GH to block preadipocyte differentiation has been attributed to its ability to increase expression of Delta-like protein 1 (Dlk1) [2,3], a known inhibitor of adipogenesis [4]. Dlk1, also known as pref-1 [4], pG2 [5] and zona glomerulosa specific mRNA [6], contains 6 EGF-like repeat domains in the extracellular domain, a transmembrane domain and a short cytoplasmic tail. It is cleaved by a yet unidentified protease to release a soluble circulating peptide containing the EGF-like repeats [7][8][9][10]; but its function remains elusive.…”

Section: Introductionmentioning

confidence: 99%

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Regulation of growth hormone expression by Delta-like protein 1 (Dlk1)

Ansell

Zhou

Schjeide

et al. 2007

Molecular and Cellular Endocrinology

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Delta-like protein 1 (Dlk1) is a transmembrane protein characterized by epidermal growth factor (EGF)-like repeats. Dlk1, which is also known as preadipocyte factor 1 (pref-1) because of its ability to inhibit preadipocyte differentiation, regulates the differentiation of several other cell types through unknown mechanisms. To elucidate Dlk1 functions, identification of Dlk1-regulated target genes is critical. The observation that Dlk1 is expressed in many endocrine tissues suggests that Dlk1 may have endocrine-related functions. Because Dlk1 is expressed in GH producing cells, we hypothesize that one function of Dlk1 is to regulate GH expression. We found that GH mRNA, protein, and secretion were significantly decreased in GH3 pituitary cell clones that stably express Dlk1. In contrast, Dlk1 expression was unable to alter prolactin expression. Co-transfection of GH3 cells with a GH promoter-regulated reporter gene showed that Dlk1 repressed GH promoter activity. Deletion and mutation analysis of the GH promoter indicated that Pit-1 binding sites in the GH promoter are required for Dlk1-mediated repression. Furthermore, Dlk1 expression represses Pit-1-mediated transcription when both proteins are co-expressed in MCF-7 cells. Deletion analysis of Dlk1 revealed that the ability of Dlk1 to regulate GH promoter activity is independent of both its EGF-like repeats and its ability to modulate MAP kinase activity. The observation that Dlk1 regulates GH expression identifies the first endocrine function of Dlk1, establishes GH as a Dlk1-regulated target gene, and provides a model system to facilitate studies of Dlk1-mediated signaling.

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Pref-1, a protein containing EGF-like repeats, inhibits adipocyte differentiation

Cited by 617 publications

References 71 publications

Defective Myofibroblast Formation from Mesenchymal Stem Cells in the Aging Murine Heart

Defective Myofibroblast Formation from Mesenchymal Stem Cells in the Aging Murine Heart

High delta‐like 1 expression in a subset of neuroblastoma cell lines corresponds to a differentiated chromaffin cell type

Regulation of growth hormone expression by Delta-like protein 1 (Dlk1)

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