The ontogeny of TGF-β1, -β2, -β3, and TGF-β receptor-II expression in the pancreas: Implications for regulation of growth and differentiation

Crisera, Christopher A.; Rose, Michael I.; Connelly, Patrick R.; Li, Min; Colen, Kari L.; Longaker, Michael T.; Gittes, George K.

doi:10.1016/s0022-3468(99)90357-3

Cited by 39 publications

(19 citation statements)

References 20 publications

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“…TGF-␤ ligands and their signaling components have been shown to be expressed in the developing pancreas. Developing islet cells demonstrate diffuse cytoplasmic immunostaining for TGF-␤ 2 and TGF-␤ 3 , however the exocrine pancreas exhibits a greater number of acinar cells with immunoreactivity for TGF-␤ 1 than for TGF-␤ 2 or TGF-␤ 3 , and all three TGF-␤ isoforms show a similar intensity and pattern of immunostaining in ductal cells [8,9] . This differential pattern of expression for each TGF-␤ isoform suggests that this pathway is an important regulator of pancreatic organogenesis.…”

Section: Tgf-␤ Basicsmentioning

confidence: 99%

Basics of TGF-ß and Pancreatic Cancer

2007

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Section: Tgf-␤ Basicsmentioning

confidence: 99%

Basics of TGF-ß and Pancreatic Cancer

2007

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“…Expression of the TGF␤ signaling pathway components has been detected in the pancreatic epithelium and mesenchyme and in mature and developing islets. These include the ligand subunits of TGF-␤1-3, activin␤B, inhibin-␣, BMP2, BMP4, BMP5, BMP6, BMP7, GDF11, ligand antagonists such as follistatin, the receptors T␤R-II, ActR-IA, ActR-IB, ActR-IIA, ActR-IIB, BMPR-IA, BMPR-IB, BMPR-II, and intracellular mediators such as Smad2 (Ogawa et al 1993;Feijen et al 1994;Furukawa et al 1995;Verschueren et al 1995;Crisera et al 1999;Tremblay et al 2000;Dichmann et al 2003).…”

Section: Tgf-␤ Signalingmentioning

confidence: 99%

On the origin of the β cell

Oliver‐Krasinski¹,

Stoffers²

2008

Genes Dev.

334

320

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The major forms of diabetes are characterized by pancreatic islet ␤-cell dysfunction and decreased ␤-cell numbers, raising hope for cell replacement therapy. Although human islet transplantation is a cell-based therapy under clinical investigation for the treatment of type 1 diabetes, the limited availability of human cadaveric islets for transplantation will preclude its widespread therapeutic application. The result has been an intense focus on the development of alternate sources of ␤ cells, such as through the guided differentiation of stem or precursor cell populations or the transdifferentiation of more plentiful mature cell populations. Realizing the potential for cell-based therapies, however, requires a thorough understanding of pancreas development and ␤-cell formation. Pancreas development is coordinated by a complex interplay of signaling pathways and transcription factors that determine early pancreatic specification as well as the later differentiation of exocrine and endocrine lineages. This review describes the current knowledge of these factors as they relate specifically to the emergence of endocrine ␤ cells from pancreatic endoderm. Current therapeutic efforts to generate insulin-producing ␤-like cells from embryonic stem cells have already capitalized on recent advances in our understanding of the embryonic signals and transcription factors that dictate lineage specification and will most certainly be further enhanced by a continuing emphasis on the identification of novel factors and regulatory relationships.Diabetes is rapidly becoming a global epidemic, with a staggering health, societal, and economic impact. Recent estimates by the American Diabetes Association suggest that the lifetime risk of developing diabetes for Americans born in the year 2000 is one in three. Diabetes results when insulin production by the pancreatic islet ␤ cell is unable to meet the metabolic demand of peripheral tissues such as liver, fat, and muscle.A reduction in ␤-cell function and mass leads to hyperglycemia (elevated blood sugar) in both type 1 and type 2 diabetes. In type 1 diabetes, autoimmune destruction of the ␤ cell itself severely reduces ␤-cell mass, resulting in marked hypoinsulinemia and potentially lifethreatening ketoacidosis. In contrast, during the progression to type 2 diabetes, impaired ␤-cell compensation in the setting of insulin resistance (impaired insulin action) eventually leads to ␤-cell failure and a modest but significant reduction in ␤-cell mass (Maclean and Ogilvie 1955; Butler et al. 2003;Yoon et al. 2003). More recently, autoimmunity has been detected in a subset of patients with type 2 diabetes, which has led to a revision of the classification to include LADA, latent autoimmune diabetes of adulthood, underscoring the continuum between type 1 and type 2 diabetes, and raising questions as to the role of immunity and inflammation in ␤-cell dysfunction and death in type 2 diabetes (Syed et al. 2002; Pozzilli and Buzzetti 2007). Conversely, forms of ketosis prone diabetes due to sev...

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“…Its appearance and the increase of its expression in late gestational ages could be related to the pancreatic expression of transforming growth factor (TGF)-b signaling components (Kim and Hebrok 2001). In particular, TGF-b receptor II is present in the pancreatic rudiment of the mouse from E12.5, and it becomes progressively more expressed in developing ducts up to E18.5 (Crisera et al 1999). The upregulation of vimentin expression is one of several biological effects exerted by TGF-b1 (Carey and Zehner 1995), and it has recently been shown that a TGF-b1 response element is present within the activator protein complex-1 region of the vimentin promoter (Wu et al 2007).…”

Section: Discussionmentioning

confidence: 99%

An Appraisal of Intermediate Filament Expression in Adult and Developing Pancreas: Vimentin Is Expressed in α Cells of Rat and Mouse Embryos

Bella

Regoli

Nicoletti

et al. 2009

J Histochem Cytochem.

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Intermediate filaments are frequently used in studies of developmental biology as markers of cell differentiation. To assess whether they can be useful to identify differentiating pancreatic endocrine cells, we examined the pattern of expression of nestin, cyto-keratin 20, and vimentin on acetone-fixed cryosections of rat adult and developing pancreas. We also studied vimentin expression in mouse embryonic pancreas at E19. Cytokeratin 20 was found in all pancreatic epithelial cell lineages during the entire development of the rat gland and in the adult animals. Under our experimental conditions, therefore, cytokeratin 20 is not an exclusive marker of rat duct cells. Nestin was detected exclusively in stromal cells either in the adult or developing rat pancreas. Vimentin was observed within cells located in the primitive ducts of rat pancreas starting from E12.5. Their number rapidly increased, reaching its highest level in newborn animals. Vimentin was also spotted in α cells starting from E12.5 but disappeared soon after birth, likely identifying immature or recently differentiated α cells. In addition, vimentin was observed in duct and α cells of mouse developing pancreas showing that its expression in such cells is not an event restricted to the rat. This manuscript contains online supplemental material at http://www.jhc.org . Please visit this article online to view these materials.

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The ontogeny of TGF-β1, -β2, -β3, and TGF-β receptor-II expression in the pancreas: Implications for regulation of growth and differentiation

Cited by 39 publications

References 20 publications

Basics of TGF-ß and Pancreatic Cancer

Basics of TGF-ß and Pancreatic Cancer

On the origin of the β cell

An Appraisal of Intermediate Filament Expression in Adult and Developing Pancreas: Vimentin Is Expressed in α Cells of Rat and Mouse Embryos

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