Impaired liver regeneration in aged mice can be rescued by silencing Hippo core kinases MST1 and MST2
Abstract
The liver has an intrinsic capacity to regenerate in response to injury or surgical resection. Nevertheless, circumstances in which hepatocytes are unresponsive to proliferative signals result in impaired regeneration and hepatic failure. As the Hippo pathway has a canonical role in the maintenance of liver size, we investigated whether it could serve as a therapeutic target to support regeneration. Using a standard two‐thirds partial hepatectomy (PH) model in young and aged mice, we demonstrate that the Hippo pathway is modulated across the phases of liver regeneration. The activity of the core kinases MST1 and...
Source: EMBO Molecular Medicine - November 30, 2016 Category: Molecular Biology Authors: Giulio Loforese, Thomas Malinka, Adrian Keogh, Felix Baier, Cedric Simillion, Matteo Montani, Thanos D Halazonetis, Daniel Candinas, Deborah Stroka Tags: Research Article Source Type: research
Activin promotes skin carcinogenesis by attraction and reprogramming of macrophages
Abstract
Activin has emerged as an important player in different types of cancer, but the underlying mechanisms are largely unknown. We show here that activin overexpression is an early event in murine and human skin tumorigenesis. This is functionally important, since activin promoted skin tumorigenesis in mice induced by the human papillomavirus 8 oncogenes. This was accompanied by depletion of epidermal γδ T cells and accumulation of regulatory T cells. Most importantly, activin increased the number of skin macrophages via attraction of blood monocytes, which was prevented by depletion of CCR2‐positive monocytes. G...
Source: EMBO Molecular Medicine - November 30, 2016 Category: Molecular Biology Authors: Maria Antsiferova, Aleksandra Piwko ‐Czuchra, Michael Cangkrama, Mateusz Wietecha, Dilara Sahin, Katharina Birkner, Valerie C Amann, Mitchell Levesque, Daniel Hohl, Reinhard Dummer, Sabine Werner Tags: Research Article Source Type: research
Gut flora connects obesity with pathological angiogenesis in the eye
Neovascular age‐related macular degeneration (nvAMD) can cause severe vision loss among the elderly. Genetic risk factors for AMD include several variants related to the immune system and lipid metabolism. Obesity is a well‐known predisposing factor for nvAMD but how this metabolic disorder modulates angiogenesis in the posterior eye segment was largely unknown. In this issue of EMBO Molecular Medicine, Andriessen et al () show that high‐fat diet‐induced obesity causes dysbiosis in the gut that drives retinal inflammation and pathological angiogenesis in a mouse model of laser‐induced choroidal neovascularizatio...
Source: EMBO Molecular Medicine - November 14, 2016 Category: Molecular Biology Authors: Rebecca Scholz, Thomas Langmann Tags: News & Views Source Type: research
4 ‐Aminopyridine promotes functional recovery and remyelination in acute peripheral nerve injury
Abstract
Traumatic peripheral nerve damage is a major medical problem without effective treatment options. In repurposing studies on 4‐aminopyridine (4‐AP), a potassium channel blocker that provides symptomatic relief in some chronic neurological afflictions, we discovered this agent offers significant promise as a small molecule regenerative agent for acute traumatic nerve injury. We found, in a mouse model of sciatic crush injury, that sustained early 4‐AP administration increased the speed and extent of behavioral recovery too rapidly to be explained by axonal regeneration. Further studies demonstrated that 4‐AP...
Source: EMBO Molecular Medicine - November 13, 2016 Category: Molecular Biology Authors: Kuang ‐Ching Tseng, Haiyan Li, Andrew Clark, Leigh Sundem, Michael Zuscik, Mark Noble, John Elfar Tags: Research Article Source Type: research
Lysosomal dysfunction disrupts presynaptic maintenance and restoration of presynaptic function prevents neurodegeneration in lysosomal storage diseases
Abstract
Lysosomal storage disorders (LSDs) are inherited diseases characterized by lysosomal dysfunction and often showing a neurodegenerative course. There is no cure to treat the central nervous system in LSDs. Moreover, the mechanisms driving neuronal degeneration in these pathological conditions remain largely unknown. By studying mouse models of LSDs, we found that neurodegeneration develops progressively with profound alterations in presynaptic structure and function. In these models, impaired lysosomal activity causes massive perikaryal accumulation of insoluble α‐synuclein and increased proteasomal degradation ...
Source: EMBO Molecular Medicine - October 31, 2016 Category: Molecular Biology Authors: Irene Sambri, Rosa D'Alessio, Yulia Ezhova, Teresa Giuliano, Nicolina Cristina Sorrentino, Vincenzo Cacace, Maria De Risi, Mauro Cataldi, Lucio Annunziato, Elvira De Leonibus, Alessandro Fraldi Tags: Research Article Source Type: research
