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Epithelial integrity in metazoan organs is maintained through the regulated proliferation and differentiation of organ-specific stem and progenitor cells. Although the epithelia of organs such as the intestine regenerate constantly and thus remain continuously proliferative, other organs, such as the mammalian urinary bladder, shift from near-quiescence to a highly proliferative state in response to epithelial injury. The cellular and molecular mechanisms underlying this injury-induced mode of regenerative response are poorly defined. Here we show in mice that the proliferative response to bacterial infection or chemical injury within the bladder is regulated by signal feedback between basal cells of the urothelium and the stromal cells that underlie them. We demonstrate that these basal cells include stem cells capable of regenerating all cell types within the urothelium, and are marked by expression of the secreted protein signal Sonic hedgehog (Shh). On injury, Shh expression in these basal cells increases and elicits increased stromal expression of Wnt protein signals, which in turn stimulate the proliferation of both urothelial and stromal cells. The heightened activity of this signal feedback circuit and the associated increase in cell proliferation appear to be required for restoration of urothelial function and, in the case of bacterial injury, may help clear and prevent further spread of infection. Our findings provide a conceptual framework for injury-induced epithelial regeneration in endodermal organs, and may provide a basis for understanding the roles of signalling pathways in cancer growth and metastasis. 相似文献
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Maria Pasztoi Agnes Bonifacius Joern Pezoldt Devesha Kulkarni Jana Niemz Juhao Yang René Teich Janina Hajek Fabio Pisano Manfred Rohde Petra Dersch Jochen Huehn 《Cellular and molecular life sciences : CMLS》2017,74(15):2839-2850
Adaptive immunity critically contributes to control acute infection with enteropathogenic Yersinia pseudotuberculosis; however, the role of CD4+ T cell subsets in establishing infection and allowing pathogen persistence remains elusive. Here, we assessed the modulatory capacity of Y. pseudotuberculosis on CD4+ T cell differentiation. Using in vivo assays, we report that infection with Y. pseudotuberculosis resulted in enhanced priming of IL-17-producing T cells (Th17 cells), whereas induction of Foxp3+ regulatory T cells (Tregs) was severely disrupted in gut-draining mesenteric lymph nodes (mLNs), in line with altered frequencies of tolerogenic and proinflammatory dendritic cell (DC) subsets within mLNs. Additionally, by using a DC-free in vitro system, we could demonstrate that Y. pseudotuberculosis can directly modulate T cell receptor (TCR) downstream signaling within naïve CD4+ T cells and Tregs via injection of effector molecules through the type III secretion system, thereby affecting their functional properties. Importantly, modulation of naïve CD4+ T cells by Y. pseudotuberculosis resulted in an enhanced Th17 differentiation and decreased induction of Foxp3+ Tregs in vitro. These findings shed light to the adjustment of the Th17-Treg axis in response to acute Y. pseudotuberculosis infection and highlight the direct modulation of CD4+ T cell subsets by altering their TCR downstream signaling. 相似文献
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A. Bodanszky M. A. Ondetti C. A. Ralofsky M. Bodanszky 《Cellular and molecular life sciences : CMLS》1971,27(11):1269-1270
Zusammenfassung Die optische Rotationsdispersion mehrer prolinreicher Oligopeptide aus dem Gift der SchlangeBothrops jararaca wurde gemessen und mit jener von Oligoprolinen verglichen. Es konnte nur eine qualitative Beziehung zwischen der angedeuteten Strukturrigidität und der biologischen Wirksamkeit der Peptide festgestellt werden.
This study was supported by a U.S. Public Health Service Grant No. 1RO1-AM-12473. ProfessorRosalia B. Frydman, Department of Biochemistry, University of Buenos Aires, Argentina, during her visit at Case Western Reserve University, participated in the experiments here reported. 相似文献
This study was supported by a U.S. Public Health Service Grant No. 1RO1-AM-12473. ProfessorRosalia B. Frydman, Department of Biochemistry, University of Buenos Aires, Argentina, during her visit at Case Western Reserve University, participated in the experiments here reported. 相似文献
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A. Bodanszky M. Bodanszky E. J. Jorpes V. Mutt M. A. Ondetti 《Cellular and molecular life sciences : CMLS》1970,26(9):948-950
Zusammenfassung Die optischen Rotationsspektren des intestinalen Hormons Cholecystokinin-Pancreozymin weisen, im Gegensatz zu denen des Secretins, auf das Fehlen bevorzugter Konformation und geben Einblick in den Zusammenhang zwischen molekularer Architektur und Hormonaktivität. 相似文献
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Zusammenfassung Durch simultane Ermittlung der totalen und der nutritiven Nierendurchblutung, sowie der PAH-Extraktion und -Sekretion, wurde festgestellt, dass während einer hämorrhagischen Hypotonie (1) der Nierenwiderstand ansteigt, (2) der relative Anteil der Markdurchblutung unverändert bleibt und (3) etwa 15% der gesamten Durchblutung in der Rinde durch arteriovenöse Anastomosen geleitet wird bzw. die peritubulären Kapillaren vermeidet. 相似文献
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A. S. Krishna Murthy Agnes B. Russfield 《Cellular and molecular life sciences : CMLS》1968,24(1):60-61
Zusammenfassung Vier oxidative Enzyme wurden in Schnitten von Diäthylstilbestrol-induzierten Nierentumoren in Syrischen Hamstern nachgewiesen. Die Aktivitäten der Bernsteinsäure- und -Hydroxybutter-Säure-Dehydrogenasen waren schwächer im Tumor als in der normalen Niere, diejenigen der Glucose-6-Phosphat- und Isocitronensäure-Dehydrogenasen dagegen stärker.
This investigation was supported by grants No. CA-06142 and No. C-6516 from The National Cancer Institute, US Public Health Service, and grant No. FR-05219 from the USPHS Division of Research Facilities and Resources. 相似文献
This investigation was supported by grants No. CA-06142 and No. C-6516 from The National Cancer Institute, US Public Health Service, and grant No. FR-05219 from the USPHS Division of Research Facilities and Resources. 相似文献