CTRP3 plays an important role in the development of collagen-induced arthritis in mice
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
Authors: Murayama, Masanori A.; Kakuta, Shigeru; Maruhashi, Takumi; Shimizu, Kenji; Seno, Akimasa; Kubo, Sachiko; Sato, Nozomi; Saijo, Shinobu; Hattori, Masahira; Iwakura, Yoichiro
Abstract
Rheumatoid arthritis (RA) is an autoimmune inflammatory disease exhibited most commonly in joints. We found that the expression of C1qtnf3, which encodes C1q/TNF-related protein 3 (CTRP3), was highly increased in two mouse RA models with different etiology. To elucidate the pathogenic roles of CTRP3 in the development of arthritis, we generated C1qtnf3(-/-) mice and examined the development of collagen-induced arthritis in these mice. We found that the incidence and severity score was higher in C1qtnf3(-/-) mice compared with wild-type (WT) mice. Histopathology of the joints was also more severe in C1qtnf3(-/-) mice. The levels of antibodies against type II collagen and pro-inflammatory cytokine mRNAs in C1qtnf3(-/-) mice were higher than WT mice. These observations indicate that CTRP3 plays an important role in the development of autoimmune arthritis, suggesting CTRP3 as a possible medicine to treat RA. (C) 2013 The Authors. Published by Elsevier Inc. All rights reserved.
Genes associated with bowel metastases in ovarian cancer
GYNECOLOGIC ONCOLOGY
Authors: Mariani, Andrea; Wang, Chen; Oberg, Ann L.; Riska, Shaun M.; Torres, Michelle; Kumka, Joseph; Multinu, Francesco; Sagar, Gunisha; Roy, Debarshi; Jung, Deok-Beom; Zhang, Qing; Grassi, Tommaso; Visscher, Daniel W.; Patel, Vatsal P.; Jin, Ling; Staub, Julie K.; Cliby, William A.; Weroha, Saravut J.; Kalli, Kimberly R.; Hartmann, Lynn C.; Kaufmann, Scott H.; Goode, Ellen L.; Shridhar, Viji
Abstract
Objective. This study is designed to identify genes and pathways that could promote metastasis to the bowel in high-grade serous ovarian cancer (OC) and evaluate their associations with clinical outcomes. Methods. We performed RNA sequencing of OC primary tumors (PTs) and their corresponding bowel metastases (n = 21 discovery set; n = 18 replication set). Differentially expressed genes (DEGs) were those expressed at least 2-fold higher in bowel metastases (BMets) than PTs in at least 30% of patients (P < .05) with no increased expression in paired benign bowel tissue and were validated with quantitative reverse transcription PCR. Using an independent OC cohort (n = 333), associations between DEGs in PTs and surgical and clinical outcomes were performed. Immunohistochemistry and mouse xenograft studies were performed to confirm the role of LRRC15 in promoting metastasis. Results. Among 27 DEGs in the discovery set, 21 were confirmed in the replication set: SFRP2, Col11A1, LRRC15, ADAM12, ADAMTS12, MFAP5, LUM, PLPP4, FAP, POSTN, GRP, MMP11, MMP13, C1QTNF3, EPYC, DIO2, KCNA1, NETO1, NTM, MYH13, and PVALB. Higher expression of more than half of the genes in the PT was associated with an increased requirement for bowel resection at primary surgery and an inability to achieve complete cytoreduction. Increased expression of LRRC15 in BMets was confirmed by immunohistochemistry and knockdown of LRRC15 significantly inhibited tumor progression in mice. Conclusions. We identified 21 genes that are overexpressed in bowel metastases among patients with OC. Our findings will help select potential molecular targets for the prevention and treatment of malignant bowel obstruction in OC. Published by Elsevier Inc.