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Xialian Xu, Xiaoyan Jiao, Nana Song, Weili Luo, Mingyu Liang, Xiaoqiang Ding, Jie Teng
Vascular endothelial cells may serve crucial roles in the development of acute kidney injury (AKI). microRNA (miR)‑21, which possesses a renal protective function has been found on vascular endothelial cells. The present study aimed to test the hypothesis that miR‑21 may protect vascular endothelial cells against injury, which may contribute to the protective effects of renal delayed ischemic preconditioning (IPC). Preconditioned (15 min ischemia) or Sham mice (not clamped) were subjected to 35 min occlusion of bilateral renal pedicles 4 days following preconditioning or Sham treatment...
September 2017: Molecular Medicine Reports
James F Colbert, Joshay A Ford, Sarah M Haeger, Yimu Yang, Kyrie L Dailey, Kristen C Allison, Viola Neudecker, Christopher M Evans, Vanessa L Richardson, Kelley S Brodsky, Sarah Faubel, Holger K Eltzschig, Eric P Schmidt, Adit A Ginde
Sepsis outcomes are heavily dependent on the development of septic organ injury, but no interventions exist to interrupt or reverse this process. microRNA-223 (miR-223) is known to be involved in both inflammatory gene regulation and host-pathogen interactions key to the pathogenesis of sepsis. The goal of this study was to determine the role of miR-223 as a mediator of septic kidney injury. Using miR-223 knockout mice and multiple models of experimental sepsis, we found that miR-223 differentially influences acute kidney injury (AKI) based on the model used...
August 1, 2017: American Journal of Physiology. Renal Physiology
Tomohiro Fujiwara, Koji Uotani, Aki Yoshida, Takuya Morita, Yutaka Nezu, Eisuke Kobayashi, Akihiko Yoshida, Takenori Uehara, Toshinori Omori, Kazuhisa Sugiu, Tadashi Komatsubara, Ken Takeda, Toshiyuki Kunisada, Machiko Kawamura, Akira Kawai, Takahiro Ochiya, Toshifumi Ozaki
BACKGROUND: Emerging evidence has suggested that circulating microRNAs (miRNAs) in body fluids have novel diagnostic and prognostic significance for patients with malignant diseases. The lack of useful biomarkers is a crucial problem of bone and soft tissue sarcomas; therefore, we investigated the circulating miRNA signature and its clinical relevance in osteosarcoma. METHODS: Global miRNA profiling was performed using patient serum collected from a discovery cohort of osteosarcoma patients and controls and cell culture media...
May 16, 2017: Oncotarget
Kostiantyn Dreval, Aline de Conti, Shinji Furuya, Frederick A Beland, Ivan Rusyn, Igor P Pogribny
Excessive alcohol consumption has a significant impact on human health and is a major public health problem worldwide. One of the consequences of long-term excessive alcohol consumption is cellular injury in almost all organs and tissues, with acute kidney injury (AKI) being one of the most common pathological manifestations. In the present study, using a mouse model of alcoholic liver fibrosis-associated AKI induced by a combined treatment with carbon tetrachloride (CCl4) and ethanol and resembling pathological features of AKI in human alcoholic liver fibrosis, we demonstrate alterations in histone modifications in the kidneys and, importantly, in the promoter region of the over-expressed SRY (sex determining region Y)-box 9 (Sox9) gene...
June 1, 2017: Toxicology
Camila Eleuterio Rodrigues, José Manuel Condor Capcha, Ana Carolina de Bragança, Talita Rojas Sanches, Priscila Queiroz Gouveia, Patrícia Aparecida Ferreira de Oliveira, Denise Maria Avancini Costa Malheiros, Rildo Aparecido Volpini, Mirela Aparecida Rodrigues Santinho, Bárbara Amélia Aparecida Santana, Rodrigo do Tocantins Calado, Irene de Lourdes Noronha, Lúcia Andrade
BACKGROUND: Mesenchymal stromal cells (MSCs) represent an option for the treatment of acute kidney injury (AKI). It is known that young stem cells are better than are aged stem cells at reducing the incidence of the senescent phenotype in the kidneys. The objective of this study was to determine whether AKI leads to premature, stress-induced senescence, as well as whether human umbilical cord-derived MSCs (huMSCs) can prevent ischaemia/reperfusion injury (IRI)-induced renal senescence in rats...
January 28, 2017: Stem Cell Research & Therapy
Kianoush Kashani, Wisit Cheungpasitporn, Claudio Ronco
Acute kidney injury (AKI) is a common complication of critical illnesses and has a significant impact on outcomes, including mortality and morbidities. Unfortunately, apart from prophylactic measures, no effective treatment for this syndrome is known. Therefore, early recognition of AKI not only can provide better opportunities for preventive interventions, but also opens many gates for research and development of effective therapeutic options. Over the last few years, several new AKI biomarkers have been discovered and validated to improve early detection, differential diagnosis, and differentiation of patients into risk groups for progressive renal failure, need for renal replacement therapy (RRT), or death...
July 26, 2017: Clinical Chemistry and Laboratory Medicine: CCLM
Lulu Zhang, Yuan Xu, Song Xue, Xudong Wang, Huili Dai, Jiaqi Qian, Zhaohui Ni, Yucheng Yan
PURPOSE: Ischemia-reperfusion injury (IRI) is a major cause of acute kidney injury (AKI) with poor outcomes. While many important functions of microRNAs (miRNAs) have been identified in various diseases, few studies reported miRNAs in acute kidney IRI, especially the dynamic changes in their expression and their implications during disease progression. METHODS: The expression of miR-192, a specific kidney-enriched miRNA, was assessed in both the plasma and kidney of IRI rats at different time points after kidney injury and compared to renal function and kidney histological changes...
March 2017: International Urology and Nephrology
Shun-Jie Chen, Ping Wu, Li-Jing Sun, Bo Zhou, Wei Niu, Shuang Liu, Fu-Jun Lin, Geng-Ru Jiang
Acute kidney injury (AKI) is a disease where kidney function is lost almost instantaneously; it can develop very rapidly over few hours to maximum of few days. Despite the advent of technology, the clinical management against this disease is very poor, and most of the time it is life-threatening. AKI has been actively regulated by extracellular matrix proteins (ECM), however, its underlying mechanism of regulation during AKI progression is very poorly understood. In this study, we explored the integrated network of mRNA and microRNAs (miRNAs) that maintains the progression of ECM after induction of AKI by lethal ischemia...
February 2017: Oncology Reports
Ping Zhou, Zhi Chen, Yan Zou, Xiaoxiao Wan
Acute kidney injury (AKI) is a complex kidney disorder that leads to numerous complications, such as elevated nitrogenous wastes, metabolic acidosis, high potassium levels and even death. The pathogenesis of AKI is very complicated, and its causes are commonly categorized as prerenal, intrinsic or postrenal. In the past few years, evidence has accumulated showing that non-coding RNAs (ncRNAs), such as microRNAs (miRNAs) and long non-coding RNAs (lncRNAs), have significant potential to aid the development of diagnostic and therapeutic strategies of AKI...
2016: Kidney & Blood Pressure Research
Nelly Rahkonen, Aki Stubb, Maia Malonzo, Sanna Edelman, Maheswara Reddy Emani, Elisa Närvä, Harri Lähdesmäki, Hannele Ruohola-Baker, Riitta Lahesmaa, Riikka Lund
MicroRNAs (miRNA) are central regulators of diverse biological processes and are important in the regulation of stem cell self-renewal. One of the widely studied miRNA-protein regulators is the Lin28-Let-7 pair. In this study, we demonstrate that contrary to the well-established models of mouse ES cells (mESC) and transformed human cancer cells, the pluripotent state of human ES cells (hESC) involves expression of mature Let-7 family miRNAs with concurrent expression of all LIN28 proteins. We show that mature Let-7 miRNAs are regulated during hESC differentiation and have opposite expression profile with LIN28B...
November 2016: Stem Cell Research
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...
September 8, 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...
November 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...
August 15, 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...
February 2017: 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...
March 2017: 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...
October 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...
2016: Nephron
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