The EDGE

Inside Lab Invest

2012 92: 1664-1665; 10.1038/labinvest.2012.165

Editorials

Beyond the RAAS: dissecting the antifibrotic effects of vitamin D analogues

Katarina Mirković and Martin H de Borst

2012 92: 1666-1669; 10.1038/labinvest.2012.150

MDR-1, Bcl-xL, H. pylori, and Wnt/β-catenin signalling in the adult stomach: how much is too much?

R John MacLeod

2012 92: 1670-1673; 10.1038/labinvest.2012.151

Research Articles

GENITOURINARY AND REPRODUCTIVE SYSTEMS

Impairment of podocyte function by diphtheria toxin—a new reversible proteinuria model in mice

Diphtheria toxin (DTx)-induced transient kidney dysfunction is presented as a new reversible model of experimental podocyte injury. Treatment of mice with DTx leads to a transient and completely reversible proteinuria as a consequence of podocyte dysfunction that is morphologically characterized by foot process fusion and detachment from the glomerular basal membrane.

Andreas Goldwich, Alexander Steinkasserer, André Gessner and Kerstin Amann

2012 92: 1674-1685; advance online publication, September 24, 2012; 10.1038/labinvest.2012.133

Maxacalcitol ameliorates tubulointerstitial fibrosis in obstructed kidneys by recruiting PPM1A/VDR complex to pSmad3

Maxacalcitol (OCT), a vitamin D analog, ameliorates tubulointerstitial fibrosis in the obstructed kidney without suppressing renal renin. OCT attenuates pSmad3- dependent production of TGF-β1 by recruiting a complex of the vitamin D receptor and pSmad3 phosphatase, PPM1A. OCT therefore serves as an inhibitor of the Smad3/TGF-β1 cycle in fibrotic kidney disease.

Kazunori Inoue, Isao Matsui, Takayuki Hamano, Naohiko Fujii, Akihiro Shimomura, Chikako Nakano, Yasuo Kusunoki, Yoshitsugu Takabatake, Michinori Hirata, Akira Nishiyama, Yoshiharu Tsubakihara, Yoshitaka Isaka and Hiromi Rakugi

2012 92: 1686-1697; advance online publication, August 27, 2012; 10.1038/labinvest.2012.107

The monocyte chemoattractant protein-1 (MCP-1)/CCR2 system is involved in peritoneal dialysis-related epithelial–mesenchymal transition of peritoneal mesothelial cells

Epithelial-mesenchymal transition (EMT) of peritoneal mesothelial cells influences development of peritoneal fibrosis (PF), a serious complication of peritoneal dialysis (PD). The monocyte chemoattractant protein-1/CCR2 system is shown to be directly involved in PD-related EMT, and extracellular matrix synthesis is mediated via TGF-β1, indicating therapeutic targets for prevention of PF.

Sun Ha Lee, Hye-Young Kang, Kyung Sik Kim, Bo Young Nam, Jisun Paeng, Seonghun Kim, Jin Ji Li, Jung Tak Park, Dong Ki Kim, Seung Hyeok Han, Tae-Hyun Yoo and Shin-Wook Kang

2012 92: 1698-1711; advance online publication, September 24, 2012; 10.1038/labinvest.2012.132

HEPATIC AND PANCREATIC AND GASTROINTESTINAL SYSTEMS

Lumican, an extracellular matrix proteoglycan, is a novel requisite for hepatic fibrosis

Lumican, a matrix proteoglycan involved in collagen fibril assembly, is upregulated in liver injury in response to TGF-β1, making it a therapeutic target for treatment of hepatic fibrosis. Lumican-null mice are protected from carbon tetrachloride-induced fibrosis by the impairment in collagen fibrillogenesis, increased matrix turnover, and an enhanced proliferative response.

Anuradha Krishnan, Xia Li, WinstonWhei-Yang Kao, Kimberly Viker, Kim Butters, Howard Masuoka, Bruce Knudsen, Gregory Gores and Michael Charlton

2012 92: 1712-1725; advance online publication, September 24, 2012; 10.1038/labinvest.2012.121

Lack of hepatic c-Met and gp130 expression is associated with an impaired antibacterial response and higher lethality after bile duct ligation

Hepatocyte growth factor/c-Met and interleukin-6/gp130 control hepatic cytoprotective pathways and show promise as therapeutic strategies for liver failure. They are involved in the hepatic antibacterial and innate immune responses and control the acute-phase response, thus preventing sepsis and liver injury during cholestatic conditions.

Arne Giebeler, Lars-Ove Brandenburg, Michaela Kaldenbach, Stephanie Erschfeld, Hermann Wasmuth, Christoph Wruck, Christian Trautwein and Konrad L Streetz

2012 92: 1726-1737; advance online publication, September 17, 2012; 10.1038/labinvest.2012.122

Salvianolic acid B lowers portal pressure in cirrhotic rats and attenuates contraction of rat hepatic stellate cells by inhibiting RhoA signaling pathway

Contraction of hepatic stellate cells (HSCs) is critical for regulation of intrahepatic vascular resistance. Salvianolic acid B (Sal B), a potential candidate for the pharmacological treatment of portal hypertension, decreases portal pressure in cirrhotic livers. Mechanistically, Sal B reduces contraction of activated HSCs by inhibiting the RhoA/ROCK II signaling pathway.

Hong Xu, Yang Zhou, Chao Lu, Jian Ping and Lie-Ming Xu

2012 92: 1738-1748; advance online publication, September 17, 2012; 10.1038/labinvest.2012.113

Lack of MMP10 exacerbates experimental colitis and promotes development of inflammation-associated colonic dysplasia

Matrix metalloproteinase MMP10, produced by infiltrating myeloid cells after colonic damage, plays a role in resolution of the disease. In the absence of this enzyme, colonic inflammation persists and eventually results in the development of dysplastic lesions. Thus, enhancing MMP10 expression may be a therapeutic strategy for promotion of mucosal healing.

Felicitas L Koller, E Ashley Dozier, Ki Taek Nam, Mei Swee, Timothy P Birkland, William C Parks and Barbara Fingleton

2012 92: 1749-1759; advance online publication, October 8, 2012; 10.1038/labinvest.2012.141

ANGIOGENESIS, CARDIOVASCULAR AND PULMONARY SYSTEMS

Pulmonary imaging with a scanning acoustic microscope discriminates speed-of-sound and shows structural characteristics of disease

Tissue elasticity can be detected using a scanning acoustic microscope, whereby acoustic images are created measuring the speed of sound through tissues. This system discriminates between pulmonary tissue components and demonstrates distinct acoustic images of the lung; the images correspond well to those obtained from a conventional microscope.

Katsutoshi Miura and Seiji Yamamoto

2012 92: 1760-1765; advance online publication, September 24, 2012; 10.1038/labinvest.2012.135

Impaired post-infarction cardiac remodeling in chronic kidney disease is due to excessive renin release

The renin-angiotensin system (RAS) has a critical role in the development of cardiorenal syndrome, the complex pathophysiological interactions between heart and kidney diseases. A novel animal model for cardiorenal syndrome suggests that nephrectomy exacerbates myocardial ischemia-induced left ventricular dysfunction, and that renin activity is responsible for adverse myocardial remodeling.

Masahito Ogawa, Jun-ichi Suzuki, Kiyoshi Takayama, Takaaki Senbonmatsu, Yasunobu Hirata, Ryozo Nagai and Mitsuaki Isobe

2012 92: 1766-1776; advance online publication, September 17, 2012; 10.1038/labinvest.2012.136

BREAST, SKIN, SOFT TISSUE AND BONE

Nordihydroguaiaretic acid inhibition of NFATc1 suppresses osteoclastogenesis and arthritis bone destruction in rats

Recruitment of osteoclasts is observed at sites of bone destruction in rheumatoid arthritis (RA). Nordihydroguaiaretic acid (NDGA) is an ancient treatment now shown to suppress osteoclast differentiation through NFATc1, a key transcription factor for osteoclastogenesis. NDGA therefore holds promise as a therapeutic agent for amelioration of inflammatory bone destruction in RA.

Yin-Ji Li, Akiko Kukita, Toshiyuki Watanabe, Toshio Takano, Pengfei Qu, Keisuke Sanematsu, Yuzo Ninomiya and Toshio Kukita

2012 92: 1777-1787; advance online publication, October 8, 2012; 10.1038/labinvest.2012.134

BRN2 is a transcriptional repressor of CDH13 (T-cadherin) in melanoma cells

Loss of cell surface glycoprotein T-cadherin has been implicated in cancer progression. Promoter hypermethylation and transcriptional repression of T-cadherin by the transcription factor BRN2 results in malignant transformation of melanoma cells, increasing invasion and migration. Regulation of T-cadherin could therefore be a focus of future melanoma therapies.

Lisa Ellmann, Manjunath B Joshi, Therese J Resink, Anja K Bosserhoff and Silke Kuphal

2012 92: 1788-1800; advance online publication, October 15, 2012; 10.1038/labinvest.2012.140

Retraction

Slug enhances invasion ability of pancreatic cancer cells through upregulation of matrix metalloproteinase-9 and actin cytoskeleton remodeling

Kejun Zhang, Dong Chen, Xuelong Jiao, Shaoyan Zhang, Xiangping Liu, Jingyu Cao, Liqun Wu and Dongsheng Wang

2012 92: 1801; advance online publication, November 19, 2012; 10.1038/labinvest.2012.138

Corrigenda

Complementary inhibition of cerebral aneurysm formation by eNOS and nNOS

Tomohiro Aoki, Masaki Nishimura, Hiroharu Kataoka, Ryota Ishibashi, Kazuhiko Nozaki and Susumu Miyamoto

2012 92: 1802; 10.1038/labinvest.2012.137

TNF gene cluster deletion abolishes lipopolysaccharide-mediated sensitization of the neonatal brain to hypoxic ischemic insult

Giles S Kendall, Mariya Hirstova, Sigrun Horn, Dimitra Dafou, Alejandro Acosta-Saltos, Beatriz Almolda, Virginia Zbarsky, Prakasham Rumajogee, Heike Heuer, Bernardo Castellano, Klaus Pfeffer, Sergei A Nedospasov, Donald M Peebles and Gennadij Raivich

2012 92: 1803; 10.1038/labinvest.2012.152