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Pei-Chun Fan, Chia-Chun Chen, Yung-Chang Chen, Yu-Sun Chang, Pao-Hsien Chu
Acute kidney injury (AKI) is an important clinical issue that is associated with significant morbidity and mortality. Despite research advances over the past decades, the complex pathophysiology of AKI is not fully understood. The regulatory mechanisms underlying post-AKI repair and fibrosis have not been clarified either. Furthermore, there is no definitively effective treatment for AKI. MicroRNAs (miRNAs) are endogenous single-stranded noncoding RNAs of 19~23 nucleotides that have been shown to be crucial to the post-transcriptional regulation of various cellular biological functions, including proliferation, differentiation, metabolism, and apoptosis...
2016: Human Genomics
Yasunori Matsumoto, Masayuki Kano, Yasunori Akutsu, Naoyuki Hanari, Isamu Hoshino, Kentaro Murakami, Akihiro Usui, Hiroshi Suito, Masahiko Takahashi, Ryota Otsuka, Hu Xin, Aki Komatsu, Keiko Iida, Hisahiro Matsubara
Exosomes play important roles in cancer progression. Although its contents (e.g., proteins and microRNAs) have been focused on in cancer research, particularly as potential diagnostic markers, the exosome behavior and methods for exosome quantification remain unclear. In the present study, we analyzed the tumor-derived exosome behavior and assessed the quantification of exosomes in patient plasma as a biomarker for esophageal squamous cell carcinoma (ESCC). A CD63-GFP expressing human ESCC cell line (TE2-CD63-GFP) was made by transfection, and mouse subcutaneous tumor models were established...
September 5, 2016: Oncology Reports
Shi-Qun Sun, Tuo Zhang, Ding Ding, Wei-Feng Zhang, Xiao-Lei Wang, Zhe Sun, Liu-Hua Hu, Sheng-Ying Qin, Ling-Hong Shen, Ben He
BACKGROUND: Contrast-induced acute kidney injury (CI-AKI) is typically defined by an increase in serum creatinine after intravascular administration of contrast medium. Because creatinine is an unreliable indicator of acute changes in kidney function, we assessed whether circulating microRNAs (miRNAs) could serve as biomarkers for early detection of CI-AKI. METHODS AND RESULTS: Using a rat model of CI-AKI, we first evaluated the miRNA profile of rat plasma and kidney...
2016: Journal of the American Heart Association
Xiangcheng Xiao, Rong Tang, Xiao Zhou, Ling Peng, Pingping Yu
Acute kidney injury (AKI) is characterized by an acute reduction in kidney function as identified by an increase in serum creatinine levels and reduction in urine output. Kidney injury molecule-1 (Kim-1) is a hallmark of kidney diseases, since it is typically non-detectable in the non-injured kidney, but upregulated and excreted in the urine during AKI. Aldosterone (Aldo) is a mediator of the renin-angiotensin-Aldo system with a pivotal role in the regulation of salt and extracellular fluid metabolism. In the present study, mice subjected to renal ischemia/reperfusion-induced AKI were investigated...
August 2016: Experimental and Therapeutic Medicine
Lucile Amrouche, Geoffroy Desbuissons, Marion Rabant, Virginia Sauvaget, Clément Nguyen, Aurélien Benon, Pauline Barre, Clémentine Rabaté, Xavier Lebreton, Morgan Gallazzini, Christophe Legendre, Fabiola Terzi, Dany Anglicheau
AKI leads to tubular injury and interstitial inflammation that must be controlled to avoid the development of fibrosis. We hypothesized that microRNAs are involved in the regulation of the balance between lesion formation and adaptive repair. We found that, under proinflammatory conditions, microRNA-146a (miR-146a) is transcriptionally upregulated by ligands of IL-1 receptor/Toll-like receptor family members via the activation of NF-κB in cultured renal proximal tubular cells. In vivo, more severe renal ischemia-reperfusion injury (IRI) associated with increased expression of miR-146a in both allografts and urine of human kidney transplant recipients, and unilateral IRI in mice induced miR-146a expression in injured kidneys...
July 21, 2016: Journal of the American Society of Nephrology: JASN
Kayo Nakamura, Masatoshi Jinnin, Miho Harada, Hideo Kudo, Wakana Nakayama, Kuniko Inoue, Aki Ogata, Ikko Kajihara, Satoshi Fukushima, Hironobu Ihn
BACKGROUND: Exosomes are small vesicles shed from various cells. They contain proteins, lipids, and nucleic acids, and are regarded as a tool of cell-cell communication. OBJECTIVES: To reveal the putative role of exosomes in systemic sclerosis (SSc), and to elucidate the effect of exosomes on wound healing. METHODS: The expression of common markers for exosomes (CD63, CD9, and CD81) and type I collagen were examined with real-time PCR, immunohistochemical analysis, ELISA, immunoblotting, and flow cytometry...
October 2016: Journal of Dermatological Science
Xue-Yan Pu, Jia-Ying Shen, Zhong-Ping Deng, Ze-An Zhang
Aristolochic acid I (AAI) derived from a natural herbal alkaloid is a nephrotoxicant. AAI-induced acute kidney injury (AKI), a devastating clinical disease associated with high mortality rates, is difficult for early diagnosis. To address this issue, we identified and validated early-detection biomarkers for AAI-induced acute kidney injury via profiling microRNA expression in rats. Global miRNA expression profile analysis found that 21 miRNAs were significantly dysregulated in kidney of rats treated by 40 mg/kg AAI on day 2, day 4, or day 6, among which 5 miRNAs were upregulated at all three time points...
July 15, 2016: Archives of Toxicology
Yuan Zhu, Jing Yu, Lei Yin, Ying Zhou, Zixuan Sun, Haoyuan Jia, Yang Tao, Wanzhu Liu, Bin Zhang, Jiao Zhang, Mei Wang, Xu Zhang, Yongmin Yan, Jianguo Xue, Hongbin Gu, Fei Mao, Wenrong Xu, Hui Qian
: : The role of mesenchymal stem cells (MSCs) in kidney injury repair has been studied widely. However, the underlying molecular mechanism remains unclear. We profiled the altered microRNAs in renal tissues from cisplatin-induced acute kidney injury (AKI) rats treated with or without rat bone marrow MSCs (rMSCs). We observed that microRNA-146b (miR-146b) expression was considerably upregulated in renal tissues from AKI rats compared with that in healthy rats, and the expression decreased following MSC treatment after cisplatin administration...
July 8, 2016: Stem Cells Translational Medicine
Shuhei Osaki, Hiroshi Tazawa, Joe Hasei, Yasuaki Yamakawa, Toshinori Omori, Kazuhisa Sugiu, Tadashi Komatsubara, Tomohiro Fujiwara, Tsuyoshi Sasaki, Toshiyuki Kunisada, Aki Yoshida, Yasuo Urata, Shunsuke Kagawa, Toshifumi Ozaki, Toshiyoshi Fujiwara
Osteosarcoma is a rare disease diagnosed as malignant bone tumor. It is generally refractory to chemotherapy, which contributes to its poor prognosis. The reversal of chemoresistance is a major clinical challenge to improve the prognostic outcome of osteosarcoma patients. We developed a tumor-specific replication-competent oncolytic adenovirus, OBP-301 (telomelysin) and assessed its synergistic effects with chemotherapeutic agents (cisplatin and doxorubicin) using human osteosarcoma cell lines and a xenograft tumor model...
2016: Scientific Reports
Zhiwen Liu, Shixuan Wang, Qing-Sheng Mi, Zheng Dong
MicroRNAs (miRNAs) are small non-coding RNAs that regulate gene expression mainly by repressing their target gene translation. A large spectrum of human diseases is associated with significant changes in miRNAs. Many miRNAs are induced in diseases, whereas some others are downregulated. The significance of miRNAs has been demonstrated in renal development and physiology, and in major kidney diseases such as acute kidney injury (AKI). Recent studies have further implicated specific miRNAs in the pathogenesis of AKI...
June 21, 2016: Nephron
Hsi-Hsien Chen, Yi-Fan Lan, Hsiao-Fen Li, Ching-Feng Cheng, Pei-Fang Lai, Wei-Hua Li, Heng Lin
Ischemia-reperfusion (I/R) induced acute kidney injury (AKI) is regulated by transcriptional factors and microRNAs (miRs). However, modulation of miRs by transcriptional factors has not been characterized in AKI. Here, we found that urinary miR-16 was 100-fold higher in AKI patients. MiR-16 was detected earlier than creatinine in mouse after I/R. Using TargetScan, the 3'UTR of B-cell lymphoma 2 (BCL-2) was found complementary to miR-16 to decrease the fluorescent reporter activity. Overexpression of miR-16 in mice significantly attenuated renal function and increased TUNEL activity in epithelium tubule cells...
2016: Scientific Reports
Claire Francoz, Mitra K Nadim, François Durand
Impaired renal function due to acute kidney injury (AKI) and/or chronic kidney diseases (CKD) is frequent in cirrhosis. Recurrent episodes of AKI may occur in end-stage cirrhosis. Differential diagnosis between functional (prerenal and hepatorenal syndrome) and acute tubular necrosis (ATN) is crucial. The concept that AKI and CKD represent a continuum rather than distinct entities, is now emerging. Not all patients with AKI have a potential for full recovery. Precise evaluation of kidney function and identification of kidney changes in patients with cirrhosis is central in predicting reversibility...
October 2016: Journal of Hepatology
Wanzhe Zhang, Liliang Shu
Renal ischemia-reperfusion (I/R) injury can be caused by cardiac surgery, renal vascular obstruction, and kidney transplantation, mainly leading to acute kidney injury (AKI), which is complicated by lack of effective preventative and therapeutic strategies. Ghrelin has recently been reported to possess anti-inflammatory properties in several types of cells; however, little attention has been given to the role of ghrelin in I/R-induced AKI. The aim of this study is to explore the role of ghrelin in I/R-induced AKI...
August 2016: DNA and Cell Biology
Kinya Okamoto, Masahiko Koda, Toshiaki Okamoto, Takumi Onoyama, Kenichi Miyoshi, Manabu Kishina, Jun Kato, Shiho Tokunaga, Taka-Aki Sugihara, Yuichi Hara, Keisuke Hino, Yoshikazu Murawaki
BACKGROUND & AIMS: Simple steatosis (SS) and non-alcoholic steatohepatitis (NASH) are subtypes of non-alcoholic fatty liver disease (NAFLD), and the pathogenic differences between SS and NASH remain unclear. MicroRNAs (miRNAs) are endogenous, non-coding, short RNAs that regulate gene expression. The aim of this study was to use animal models and human samples to examine the relationship between miRNA expression profiles and each type of NAFLD (SS and NASH). METHODS: DD Shionogi, Fatty Liver Shionogi (FLS) and FLS ob/ob mice were used as models for normal control, SS and NASH, respectively...
2016: PloS One
Mira Pavkovic, Cassianne Robinson-Cohen, Alicia S Chua, Oana Nicoara, Mariana Cárdenas-González, Vanesa Bijol, Krithika Ramachandran, Lucy Hampson, Munir Pirmohamed, Daniel J Antoine, Gyorgy Frendl, Jonathan Himmelfarb, Sushrut S Waikar, Vishal S Vaidya
Drug-induced acute kidney injury (AKI) is often encountered in hospitalized patients. Although serum creatinine (SCr) is still routinely used for assessing AKI, it is known to be insensitive and nonspecific. Therefore, our objective was to evaluate kidney injury molecule 1 (KIM-1) in conjunction with microRNA (miR)-21, -200c, and -423 as urinary biomarkers for drug-induced AKI in humans. In a cross-sectional cohort of patients (n = 135) with acetaminophen (APAP) overdose, all 4 biomarkers were significantly (P < ...
July 2016: Toxicological Sciences: An Official Journal of the Society of Toxicology
Xiaobing Zhou, Zhe Qu, Cong Zhu, Zhi Lin, Yan Huo, Xue Wang, Jufeng Wang, Bo Li
MicroRNAs (miRNAs) have been recently recognized as promising non-invasive biomarkers for detecting the organ injuries. To further understand the sensibility and reliability of miRNA measurements in urine sample for predicting drug-induced early nephrotoxicity, a global urinary miRNA expression analysis was performed in the rodent models with gentamicin-induced acute kidney injury (AKI). Male Wistar rats were daily administrated with gentamicin (0, 60, and 120 mg/kg) for up to 10 days by intraperitoneal injection, and the miRNA profiling of animal urine samples were subsequently analyzed using TaqMan(®) Array Rodent miRNA Cards...
July 2016: Regulatory Toxicology and Pharmacology: RTP
Qingqing Wei, Yong Liu, Pengyuan Liu, Jielu Hao, Mingyu Liang, Qing-Sheng Mi, Jian-Kang Chen, Zheng Dong
MicroRNAs have been implicated in ischemic AKI. However, the specific microRNA species that regulates ischemic kidney injury remains unidentified. Our previous microarray analysis revealed microRNA-489 induction in kidneys of mice subjected to renal ischemia-reperfusion. In this study, we verified the induction of microRNA-489 during ischemic AKI in mice and further examined the underlying mechanisms. Hypoxia-inducible factor-1α deficiency associated with diminished microRNA-489 induction in cultured rat proximal tubular cells subjected to hypoxia and kidney tissues of mice after renal ischemia-reperfusion injury...
September 2016: Journal of the American Society of Nephrology: JASN
Wen Qin, Wei Xie, Xi Yang, Ning Xia, Kunling Yang
BACKGROUND: Acute kidney injury (AKI) is quite common in the patients who frequently use the anticancer drug cisplatin. microRNAs (miRNAs) are powerful tools in modulating the expression of key factors in disease progression, but little is known about roles of miRNAs in AKI. This study explored the expression and function of miR-449 in cisplatin-induced AKI. MATERIAL/METHODS: Rat renal proximal tubular cell line NRK-52E was used for cisplatin treatment and miR-449 sponge transfection...
2016: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
Rui Cui, Jia Xu, Xiao Chen, Wenliang Zhu
MicroRNAs (miRNAs) are negative regulators of gene expression and protein abundance. Current evidence shows an association of miRNAs with acute kidney injury (AKI) leading to substantially increased morbidity and mortality. Here, we investigated whether miRNAs are inductive regulators responsible for the pathological development of AKI. Microarray analysis was used to detect temporal changes in global miRNA expression within 48 h after AKI in mice. Results indicated that global miRNA expression gradually increased over 24 h from ischemia reperfusion injury after 24 h, and then decreased from 24 h to 48 h...
2016: PeerJ
Luise Gaede, Christoph Liebetrau, Johannes Blumenstein, Christian Troidl, Oliver Dörr, Won-Keun Kim, Karl Gottfried, Sandra Voss, Alexander Berkowitsch, Thomas Walther, Holger Nef, Christian W Hamm, Helge Möllmann
BACKGROUND: Acute kidney injury (AKI) is a complication after major cardiac surgery that is associated with higher rates of morbidity and mortality. MicroRNA-21 (miR-21) has been described as an early biomarker for AKI. We investigated whether miR-21 is predictive of AKI and long-term mortality after cardiac surgery. METHODS: Consecutive patients (n = 115) undergoing major cardiac surgery were included. Serum creatinine was measured prior to, 4 h after, and 1, 4 and 7 days after extracorporeal circulation...
May 2016: Nephrology, Dialysis, Transplantation
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