ANGIOGENESIS, CARDIOVASCULAR AND PULMONARY SYSTEMS
Fibroblastic foci, covered with alveolar epithelia exhibiting epithelial–mesenchymal transition, destroy alveolar septa by disrupting blood flow in idiopathic pulmonary fibrosis
Fibroblastic foci in idiopathic pulmonary fibrosis damage the lung through unknown mechanisms. This study reveals that fibroblastic foci, probably derived from alveolar epithelia exhibiting epithelial-mesenchymal transition (EMT), are located between the alveolar epithelia and capillary vessels and disrupt blood flow to alveolar septa, thereby destroying them. The authors also demonstrate that normal alveolar epithelial cells undergo dynamic EMT in vitro in response to transforming growth factor-β signaling.
Inhibition of infarction-induced sympathetic innervation with endothelin receptor antagonism via a PI3K/GSK-3β-dependent pathway
Endothelin-1 upregulates nerve growth factor expression. This study describes the role of PI3K/Akt/GSK-3β activity in upstream signaling of endothelin-1-induced sympathetic hyperinnervation. An endothelin A receptor antagonist can restore PI3K/Akt activity, which correlates with the changes in downstream nerve growth factor expression. Therefore, endothelin A receptor antagonism mediates attenuated sympathetic hyperinnervation through restoration of the PI3K/Akt/GSK-3β pathway, indicating a potential pharmacological target for arrhythmias after infarction.
T-M Lee, Nen-Chung Chang and Shinn-Zong Lin
2017 97: 243-255; advance online publication, December 19, 2016; 10.1038/labinvest.2016.138
Thy-1 interaction with Fas in lipid rafts regulates fibroblast apoptosis and lung injury resolution
Thy-1, via its glycophosphatidylinositol anchor and lipid raft localization, regulates fibroblast apoptosis via Fas-, Bcl-, and caspase-dependent pathways. Thy-1 null mice fail to resolve bleomycin-induced lung fibrosis, associated with decreased myofibroblast apoptosis, suggesting that Thy-1 is necessary and sufficient to promote apoptosis in activated fibroblasts, facilitating resolution of lung fibrosis.
Xiaoqiu Liu, Simon S Wong, Carmen A Taype, Jeeyeon Kim, Tzu-Pin Shentu, Celia R Espinoza, J Cameron Finley, John E Bradley, Brian P Head, Hemal H Patel, Emma J Mah and James S Hagood
2017 97: 256-267; advance online publication, February 6, 2017; 10.1038/labinvest.2016.145
H2S inhibits pulmonary arterial endothelial cell inflammation in rats with monocrotaline-induced pulmonary hypertension
Understanding the mechanisms regulating fibroblast survival/apoptosis should lead to novel therapeutic interventions for lung fibrosis. Using a model system of monocrotaline-induced pulmonary artery hypertension, the authors show that endogenous H2S synthesis is downregulated in pulmonary arterial endothelial cells. Administration of H2S inhibits NF-κB signaling pathway activation and thereby attenuates pulmonary arterial endothelial cell inflammation.
Shasha Feng, Siyao Chen, Wen Yu, Da Zhang, Chunyu Zhang, Chaoshu Tang, Junbao Du and Hongfang Jin
2017 97: 268-278; advance online publication, December 12, 2016; 10.1038/labinvest.2016.129
Characterization of histone-related chemical modifications in formalin-fixed paraffin-embedded and fresh-frozen human pancreatic cancer xenografts using LC-MS/MS
Liquid chromatography-tandem mass spectrometry was employed to identify potential chemical modifications of histone proteins introduced during formaldehyde tissue fixation, which could be confused with defined endogenous modifications. The authors describe modifications with defined mass shift, exclusively present in formalin-fixed paraffin embedded compared to fresh frozen tumor xenograft tissue, which can be considered as formaldehyde adducts.
Monika Bauden, Theresa Kristl, Roland Andersson, György Marko-Varga and Daniel Ansari
2017 97: 279-288; advance online publication, December 12, 2016; 10.1038/labinvest.2016.134
Hepatic stimulator substance inhibits calcium overflow through the mitochondria-associated membrane compartment during nonalcoholic steatohepatitis
In this study, the authors show that overexpression of hepatic stimulator substance (HSS) protects liver from steatosis in vitro and in vivo. Moreover, the protection provided by HSS restores sarco/endoplasmic reticulum (ER) calcium ATPase activity in the mitochondria-associated ER membrane and inhibits an excessive influx of cytosolic free Ca2+ into mitochondria during ER stress, thus preserving the mitochondrial functionality and ameliorating hepatic lipotoxicity.
Fan Xiao, Jing Zhang, Can Zhang and Wei An
2017 97: 289-301; advance online publication, December 19, 2016; 10.1038/labinvest.2016.139
Cancer cell chemokines direct chemotaxis of activated stellate cells in pancreatic ductal adenocarcinoma
Recent reports implicate stromal remodeling by stellate cells in pancreatic cancer with either pro- or anti-tumorigenic roles. The mechanisms coordinating stellate cell recruitment and activation remain enigmatic. This study indicates that inflammation-directed production of tumoral CCL28 influences recruitment and spatial reorganization of stromal remodeling by stellate cells in pancreatic cancer.
Ishan Roy, Kathleen A Boyle, Emily P Vonderhaar, Noah P Zimmerman, Egal Gorse, A Craig Mackinnon, Rosa F Hwang, Janusz Franco-Barraza, Edna Cukierman, Susan Tsai, Douglas B Evans and Michael B Dwinell
2017 97: 302-317; advance online publication, January 16, 2017; 10.1038/labinvest.2016.146
Early activated hepatic stellate cell-derived paracrine molecules modulate acute liver injury and regeneration
In this paper, the authors provide the first clear evidence that early activated hepatic stellate cell-derived secretions can dramatically reduce cell death and enhance hepatocyte and adult hepatic progenitor cells proliferation in acetaminophen-induced acute liver injury. Mechanistically, HSC-derived paracrine factors down-regulate local and systemic inflammation and promote hepatocyte proliferation by enhancing pAkt pathway activity.
Wenju Chang, Lujun Song, Xiujuan Chang, Meiling Ji, Hongshan Wang, Xinyu Qin and Weixin Niu
2017 97: 318-328; advance online publication, December 19, 2016; 10.1038/labinvest.2016.130
Proof of the quantitative potential of immunofluorescence by mass spectrometry
Immunohistochemistry and immunofluorescence are widely considered to be only semiquantitative. Mass spectrometry is often considered the absolute criterion standard for protein measurement. Here the authors show that immunofluorescence can be standardized to mass spectrometry to allow truly quantitative (accurate and linear) measurement of a protein, epidermal growth factor receptor, on glass slides.
Maria I Toki, Fabiola Cecchi, Todd Hembrough, Konstantinos N Syrigos and David L Rimm
2017 97: 329-334; advance online publication, January 16, 2017; 10.1038/labinvest.2016.148
Larger core size has superior technical and analytical accuracy in bladder tissue microarray
Tissue-microarrays are critical for simultaneous analysis of large numbers of samples and patients. Cores in a tissue-microarray must accurately represent the target tissue in order to provide an effective research tool. This paper demonstrates that core size significantly impacts accuracy, where 1.0 mm cores show superior technical and analytical accuracy over smaller 0.6 mm cores.
Adel RH Eskaros, Shanna A Arnold Egloff, Kelli L Boyd, Joyce E Richardson, M Eric Hyndman and Andries Zijlstra
2017 97: 335-342; advance online publication, January 23, 2017; 10.1038/labinvest.2016.151
Establishment and characterization of BHD-F59RSVT, an immortalized cell line derived from a renal cell carcinoma in a patient with Birt–Hogg–Dubé syndrome
The authors established a new renal cell carcinoma cell line, BHD-F59RSVT, from a typical chromophobe renal cell carcinoma that developed in a patient with Birt-Hogg-Dubé Syndrome. Detailed cytogenetic and microscopic features of BHD-F59RSVT and its original tumor are described in this paper. BHD-F59RSVT has a heterozygous FLCN mutation, and the expression of its protein product, the tumor suppressor folliculin, is markedly suppressed.
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