Laboratory Investigation - Table of Contents alert Volume 92 Issue 5

TABLE OF CONTENTS Volume 92, Issue 5 (May 2012) In this issue Inside LI Research Articles Corrigendum Also new AOP Sign up for e-alerts Recommend to your library Web feed Subscribe Advertisement May editor's recommendation from LI: Gα12 activation in podocytes leads to cumulative changes in glomerular collagen expression, proteinuria and glomerulosclerosis Little is known about the signaling mechanisms that lead to progression of glomerulosclerosis, a common pathological finding in patients with progressive chronic kidney disease that often leads to end-stage renal disease. Ilene Boucher and colleagues targeted activated Gα subunits in specific cells in vivo to identify downstream effector pathways independent of receptor activation. The findings indicate that Gα12 activation in podocytes leads to dysregulated collagen (α)IV expression, and support a model of altered glomerular structure and function resulting from persistent activation of GPCR-Gα12 signaling pathways.   Inside LI Top Inside Lab Invest 2012 92: 648-649; 10.1038/labinvest.2012.66 Full Text Research Articles Top GENITOURINARY AND REPRODUCTIVE SYSTEMS Loss of angiotensin-converting enzyme 2 enhances TGF-β/Smad-mediated renal fibrosis and NF-κB-driven renal inflammation in a mouse model of obstructive nephropathy The renin-angiotensin system is critical in chronic kidney disease. The protective role of Ace2 in intrarenal Ang II-mediated renal injury in obstructive nephropathy is examined. Deletion of Ace2 results in a 4-fold increase in the intrarenal Ang II/Ang 1-7 ratio, enhanced TGF-β/Smad2/3-mediated renal fibrosis, and NF-κB-driven renal inflammation via the Smurf2-dependent degradation of renal Smad7. Zhen Liu, Xiao Ru Huang, Hai-Yong Chen, Josef M Penninger and Hui Yao Lan 2012 92: 650-661; advance online publication, February 13, 2012; 10.1038/labinvest.2012.2 Abstract | Full Text Gα12 activation in podocytes leads to cumulative changes in glomerular collagen expression, proteinuria and glomerulosclerosis Constitutive activation of the G protein Gα12 in podocytes promotes proteinuria and glomerulosclerosis through a novel mechanism involving changes in collagen (α)IV expression without podocyte depletion. Thus, persistent G-protein-coupled receptor activation can lead to glomerular damage. Ilene Boucher, Wanfeng Yu, Sarah Beaudry, Hideyuki Negoro, Mei Tran, Martin R Pollak, Joel M Henderson and Bradley M Denker 2012 92: 662-675; advance online publication, January 16, 2012; 10.1038/labinvest.2011.198 Abstract | Full Text Wnt signaling induces epithelial–mesenchymal transition with proliferation in ARPE-19 cells upon loss of contact inhibition Proliferation and epithelial-mesenchymal transition (EMT) of retinal pigment epithelium (RPE) are hallmarks of proliferative vitreoretinopathy, but the mechanisms involved have been obscure. Treatment of RPE cells with EGTA, EGF and FGF-2 causes EMT and proliferation accompanied by canonical Wnt signaling. EGTA with TGF-β1 also leads to EMT, but suppresses proliferation and Wnt signaling. Hung-Chi Chen, Ying-Ting Zhu, Szu-Yu Chen and Scheffer CG Tseng 2012 92: 676-687; advance online publication, March 5, 2012; 10.1038/labinvest.2011.201 Abstract | Full Text Reduction of NOTCH1 expression pertains to maturation abnormalities of keratinocytes in squamous neoplasms Notch1 is expressed dominantly in the basal cells of squamous epithelium and is downregulated in squamous neoplasms of oral mucosa, esophagus and uterine cervix. Reduction of Notch1 expression alters the mature epithelium into an immature one, playing a major role in the histopathogenesis of epithelial dysplasia. Kei Sakamoto, Takuma Fujii, Hiroshi Kawachi, Yoshio Miki, Ken Omura, Kei-ichi Morita, Kou Kayamori, Ken-ichi Katsube and Akira Yamaguchi 2012 92: 688-702; advance online publication, February 13, 2012; 10.1038/labinvest.2012.9 Abstract | Full Text HEPATIC AND PANCREATIC SYSTEMS Heparin-binding epidermal growth factor-like growth factor suppresses experimental liver fibrosis in mice Endogenous production of heparin-binding epidermal growth factor-like growth factor (HB-EGF) in the liver suppresses hepatic fibrosis and reduces expression of markers of activation and fibrogenesis. The natural suppressive effects of HB-EGF have potential therapeutic implications and expand its repertoire of cytoprotective actions. Guangcun Huang, Gail E Besner and David R Brigstock 2012 92: 703-712; advance online publication, February 13, 2012; 10.1038/labinvest.2012.3 Abstract | Full Text Caspase-1-mediated regulation of fibrogenesis in diet-induced steatohepatitis During development of nonalcoholic steatohepatitis (NASH), activation of Kupffer cells results in induction of pro-inflammatory signaling and hepatic stellate cell activation, which are then responsible for collagen deposition and fibrosis. These data provide new insights into the pathogenesis of liver damage in NASH, and identify potential molecular targets for therapeutic intervention. Laura J Dixon, Michael Berk, Samjhana Thapaliya, Bettina G Papouchado and Ariel E Feldstein 2012 92: 713-723; advance online publication, March 12, 2012; 10.1038/labinvest.2012.45 Abstract | Full Text The chemokine receptor CXCR3 limits injury after acute toxic liver damage The chemokine receptor CXCR3 critically regulates migration of NK and NKT cells during acute liver injury. In CXCR3−/− mice, reduced numbers of these cells are associated with reduced hepatocyte apoptosis; but the release of HMGB1 from the necrotic liver recruits neutrophils to the injured tissue, thereby augmenting the damage. The results demonstrate an unexpected beneficial role of CXCR3 in acute toxic liver injury. Mirko Moreno Zaldivar, Marie-Luise Berres, Hacer Sahin, Andreas Nellen, Daniel Heinrichs, Petra Schmitz, Nicolaus Gassler, Konrad L Streetz, Christian Trautwein and Hermann E Wasmuth 2012 92: 724-734; advance online publication, March 19, 2012; 10.1038/labinvest.2012.48 Abstract | Full Text BREAST, SKIN, SOFT TISSUE AND BONE FOSL1 as a candidate target gene for 11q12 rearrangements in desmoplastic fibroblastoma Desmoplastic fibroblastoma is a benign soft tissue tumor with consistent rearrangement of chromosome band 11q12, strongly suggesting that this region harbors a gene of pathogenetic importance. FOSL1, a leucine zipper protein that is part of the transcription factor complex AP-1, appears to be a target for these rearrangements. Gemma Macchia, Domenico Trombetta, Emely Möller, Fredrik Mertens, Clelia T Storlazzi, Maria Debiec-Rychter, Raf Sciot and Karolin H Nord 2012 92: 735-743; advance online publication, March 12, 2012; 10.1038/labinvest.2012.46 Abstract | Full Text ORAL AND GASTROINTESTINAL SYSTEMS Snail overexpression induces an epithelial to mesenchymal transition and cancer stem cell-like properties in SCC9 cells Overexpression of Snail induces the tongue carcinoma SCC9 cell line to undergo epithelial to mesenchymal transition. These cells are then highly invasive but not highly proliferative and exhibit cancer stem cell-like properties. These novel observations may help develop new treatments for oral squamous cell carcinoma. Li-Fang Zhu, Yong Hu, Cong-Chong Yang, Xiao-Hui Xu, Tian-Yun Ning, Zi-Lu Wang, Jin-Hai Ye and Lai-Kui Liu 2012 92: 744-752; advance online publication, February 20, 2012; 10.1038/labinvest.2012.8 Abstract | Full Text Activation of transient receptor potential vanilloid subtype 1 increases expression and permeability of tight junction in normal and hyposecretory submandibular gland Activation of transient receptor potential vanilloid subtype 1 (TRPV1) increases tight junction permeability and selectively upregulates expression of ZO-1, claudin-3, and -11 in cultured rabbit submandibular gland cells and in hyposecretory, transplanted glands. Therefore, TRPV1 might be a potential target to modulate secretion of the submandibular gland under both physiological and pathophysiological conditions. Xin Cong, Yan Zhang, Liang Shi, Ning-Yan Yang, Chong Ding, Jing Li, Qian-Wen Ding, Yun-Chao Su, Ruo-Lan Xiang, Li-Ling Wu and Guang-Yan Yu 2012 92: 753-768; advance online publication, March 5, 2012; 10.1038/labinvest.2012.12 Abstract | Full Text Experimental colitis alters expression of 5-HT receptors and transient receptor potential vanilloid 1 leading to visceral hypersensitivity in mice Increased expression of neuronal/non-neuronal transient receptor potential vanilloid type 1 (TRPV1) channels and 5-hydroxytryptamine (5-HT)3 receptors, and decreased expression of 5-HT4 receptors is observed in the mucosa in a colitis-induced mouse model. The findings suggest that 5-HT receptors and TRPV1 channels, in addition to 5-HT, affect the pathology of inflammatory bowel disease. Kenjiro Matsumoto, Mee Wah Lo, Takuji Hosoya, Kimihito Tashima, Hiromitsu Takayama, Toshihiko Murayama and Syunji Horie 2012 92: 769-782; advance online publication, February 13, 2012; 10.1038/labinvest.2012.14 Abstract | Full Text Neutrophil priming by hypoxic preconditioning protects against epithelial barrier damage and enteric bacterial translocation in intestinal ischemia/reperfusion Intestinal ischemia/reperfusion (I/R) induces mucosal barrier dysfunction and bacterial translocation (BT). Neutrophil priming by hypoxic preconditioning protects against I/R-induced BT via direct antimicrobial activity by oxidative respiratory bursts and through promotion of epithelial barrier integrity for luminal confinement of enteric bacteria. Yen-Zhen Lu, Chi-Chin Wu, Yi-Chen Huang, Ching-Ying Huang, Chung-Yi Yang, Tsung-Chun Lee, Chau-Fong Chen and Linda Chia-Hui Yu 2012 92: 783-796; advance online publication, February 27, 2012; 10.1038/labinvest.2012.11 Abstract | Full Text Corrigendum Top Angiotensin II-dependent Src and Smad1 signaling pathway is crucial for the development of diabetic nephropathy Akira Mima, Takeshi Matsubara, Hidenori Arai, Hideharu Abe, Kojiro Nagai, Hiroshi Kanamori, Eriko Sumi, Toshikazu Takahashi, Noriyuki Iehara, Atsushi Fukatsu, Toru Kita and Toshio Doi 2012 92: 797; 10.1038/labinvest.2012.79 Full Text Advertisement Laboratory Investigation Web Focus: Renal Pathology Kidney disease affects over 26 million Americans, resulting in a high demand for elucidating the pathways that lead to renal pathologies and identifying potential therapeutic targets. In this web focus presented by Laboratory Investigation, recent research in the field of renal pathology is highlighted, FREE for a limited time. 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