Characterization of AT1 and AT2 receptor expression profiles in human skin during fetal life

Liu, Hongwei; Fu, Xiaobing; Li, Jianfu; Sun, Tong-zhu

doi:10.1016/j.jdermsci.2007.02.008

Cited by 8 publications

(6 citation statements)

References 8 publications

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“…The present study provided evidence that RAS components, notably AT 2 receptors, are present in the developing mouse pancreas, and we have documented up‐regulated expression of AT 2 receptors in the developing pancreas, suggesting its likely involvement in regulation of pancreatic development. Our observation that the AT 2 receptor was selectively up‐regulated in the fetal pancreas is consistent with previous reports of differential expression of AT 1 and AT 2 receptors in other developing fetal tissues (Norwood et al, ; Liu et al, ). As shown, Ngn 3 and insulin expressing cells during the critical time window for β‐cell development (E15.5 onward) were localized to a majority (<80%) of AT 2 receptor expressing cells; these data reflect, to some extent, a major role of the AT 2 receptor within the endocrine cell lineage and, in particular, in β‐cells, a postulate supported by the gradual decrease in AT 2 receptor expression after E15.5 to nearly undetectable levels in adult islets.…”

Section: Discussionsupporting

confidence: 93%

“…One such potential regulatory mechanism is the renin-angiotensin system (RAS). Expression of RAS components has been confirmed in several types of tissue progenitors (Perlegas et al, 2005;Liu et al, 2007;Contrepas et al, 2007). In human embryos, detection of RAS components is reported mainly in the heart, liver, and primitive kidney tissues starting from the 3rd to the 4th gestational weeks (Sch€ utz et al, 1996).…”

Section: Introductionmentioning

confidence: 95%

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Angiotensin II type 2 receptor regulates the development of pancreatic endocrine cells in mouse embryos

Leung

Liang

Zhao

et al. 2013

Developmental Dynamics

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Background: We previously identified a local renin-angiotensin system (RAS) regulating the differentiation of an isolated population of human pancreatic progenitor cells. Major RAS components that regulate organogenesis have been also described in embryos; however, it is not known whether a local RAS is present in the fetal pancreas. We now hypothesize that angiotensin II type 1 (AT 1 ) and type 2 (AT 2 ) receptors are expressed in mouse embryonic pancreas and involved in regulating endocrine cell development. Results: Differential expression of AT 1 and AT 2 receptors was observed in the mouse pancreata in late embryogenesis. Systemic AT 2 , but not AT 1 , receptor blockade during the second transition in pancreatic development (from embryonic day 12.0 onward) reduced the b-cell to a-cell ratio of the neonate islets, impaired their insulin secretory function and the glucose tolerance of the pups. Studies with pancreas explants ex vivo revealed regulation by AT 2 receptors of the differentiation of pancreatic progenitors into insulin-producing cells and of the proliferation of the differentiated cell, actions that did not result from reduced angiogenesis as a secondary effect of AT 2 receptor antagonism. Conclusions: These data revealed an AT 2 receptor-mediated mechanism regulating pancreatic endocrine cell development in vivo. Developmental Dynamics 243:415-427, 2014. V C 2013 Wiley Periodicals, Inc.Key words: renin-angiotensin system; fetal pancreas; islet; insulin Key findings:Differential expression of AT 1 and AT 2 receptors was identified in mouse pancreas during pancreatic development. AT 2 receptor, but not AT 1 receptor, blockade during the second transition stage of pancreatic development altered islet cell composition and impaired both insulin secretory function of neonatal islets and glucose tolerance of the pups. Pancreas explants ex vivo data showed that AT 2 receptors were essential for the differentiation of pancreatic progenitors into insulin producing cells, as well as for proliferation of the differentiated cells. No evidence was found to suggest that AT 2 receptor regulation of b-cell development is a secondary effect of angiotensin II-induced vascular endothelial growth factor-driven angiogenesis.

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Section: Discussionsupporting

confidence: 93%

Section: Introductionmentioning

confidence: 95%

Angiotensin II type 2 receptor regulates the development of pancreatic endocrine cells in mouse embryos

Leung

Liang

Zhao

et al. 2013

Developmental Dynamics

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“…8,9,18,22,23 In the present study, we demonstrated for the first time that ACE is expressed in the primitive epidermis, which is composed of two or three epidermal cell layers at 11 weeks of gestation, and is largely confined to the basal layer of the fetal epidermis from 21 weeks of gestation in humans. In addition, we observed that there is a clear colocalization of ACE with b1-integrin, K19 and p63, the putative epidermal stem cell markers, in human skin.…”

Section: Discussionsupporting

confidence: 53%

Characterization of angiotensin-converting enzyme expression during epidermis morphogenesis in humans: a potential marker for epidermal stem cells

Hw¹,

Jf²,

Huang³

et al. 2009

British Journal of Dermatology

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“…The growth and differentiation of human embryonic stem cells or mesenchymal stem cells as well as a number of progenitors including kidney, skin, or hematopoietic tissues were found to express and be regulated by major RAS components. These components include the precursor peptide angiotensinogen, the two critical enzymes renin and angiotensin‐converting enzyme (ACE), and the active peptide angiotensin II (Ang II) as well as Ang II type 1 and 2 (AT 1 and AT 2 ) receptors [7–11]. In fact, RAS components are expressed early in diverse developing tissues of human embryos.…”

Section: Introductionmentioning

confidence: 99%

Angiotensin II Type 2 Receptor Is Critical for the Development of Human Fetal Pancreatic Progenitor Cells into Islet‐like Cell Clusters and Their Potential for Transplantation

et al. 2012

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Local renin-angiotensin systems (RASs) regulate the differentiation of tissue progenitors. However, it is not known whether such systems can regulate the development of pancreatic progenitor cells (PPCs). To address this issue, we characterized the expression profile of major RAS components in human fetal PPC preparations and examined their effects on the differentiation of PPCs into functional isletlike cell clusters (ICCs). We found that expression of RAS components was highly regulated throughout PPC differentiation and that locally generated angiotensin II (Ang II) maintained PPC growth and differentiation via Ang II type 1 and type 2 (AT 1 and AT 2 ) receptors. In addition, we observed colocalization of AT 2 receptors with critical b-cell phenotype markers in PPCs/ICCs, as well as AT 2 receptor upregulation during differentiation, suggesting that these receptors may regulate b-cell development. In fact, we found that AT 2 , but not AT 1 , receptor was a key mediator of Ang II-induced upregulation of transcription factors important in b-cell development. Furthermore, lentivirusmediated knockdown of AT 2 receptor suppressed the expression of these transcription factors in ICCs. Transplantation of AT 2 receptor-depleted ICCs into immuneprivileged diabetic mice failed to ameliorate hyperglycemia, implying that AT 2 receptors are indispensable during ICC maturation in vivo. These data strongly indicate that a local RAS is involved in governing the functional maturation of pancreatic progenitors toward the endocrine lineage. STEM CELLS 2012;30:525-536 Disclosure of potential conflicts of interest is found at the end of this article.

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Characterization of AT1 and AT2 receptor expression profiles in human skin during fetal life

Cited by 8 publications

References 8 publications

Angiotensin II type 2 receptor regulates the development of pancreatic endocrine cells in mouse embryos

Angiotensin II type 2 receptor regulates the development of pancreatic endocrine cells in mouse embryos

Characterization of angiotensin-converting enzyme expression during epidermis morphogenesis in humans: a potential marker for epidermal stem cells

Angiotensin II Type 2 Receptor Is Critical for the Development of Human Fetal Pancreatic Progenitor Cells into Islet‐like Cell Clusters and Their Potential for Transplantation

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