MicroRNAs (miRNAs) are a class of posttranscriptional regulators that have recently introduced an additional level of intricacy to our understanding of gene regulation. There are currently over 10,000 miRNAs that have been identified in a range of species including metazoa, mycetozoa, viridiplantae, and viruses, of which 940, to date, are found in humans. It is estimated that more than 60% of human protein-coding genes harbor miRNA target sites in their 3' untranslated region and, thus, are potentially regulated by these molecules in health and disease. This review will first briefly describe the discovery, structure, and mode of function of miRNAs in mammalian cells, before elaborating on their roles and significance during development and pathogenesis in the various mammalian organs, while attempting to reconcile their functions with our existing knowledge of their targets. Finally, we will summarize some of the advances made in utilizing miRNAs in therapeutics.

Chronic kidney disease (CKD) is characterized by tubulointerstitial deposition of extracellular matrix, tubular atrophy and dilatation; the replacement of organ architecture by connective tissue results in progressive loss of organ function. Micro (mi)RNAs are important mediators of tissue fibrosis under various pathological conditions and are of potential therapeutic relevance. These short, noncoding nucleotides (∼22 bases) regulate target messenger RNAs at the post-transcriptional level. Several hundred miRNAs regulate a considerable amount of the human genome and are involved in virtually all biological processes, including cellular proliferation, apoptosis and differentiation. Thus, miRNA deregulation often results in impaired cellular function and development of disease. Here, we summarize the current knowledge on the role of miRNAs in CKD, with particular emphasis on hypertensive kidney disease, diabetic nephropathy, glomerular biology, and IgA nephropathy. Identification of miRNA regulation and function in renal pathology may pinpoint miRNAs as new therapeutic targets in kidney fibrosis and related diseases. A new class of RNA therapeutics, that is, miRNA modulators (such as antagomirs) have been developed, which enable specific targeting of miRNAs and respective downstream gene networks in vivo, thus influencing the mechanisms that underlie disease initiation or progression. The therapeutic potential of miRNA-based treatment strategies in CKD are discussed.

The 9th Banff Conference on Allograft Pathology was held in La Coruna, Spain on June 23-29, 2007. A total of 235 pathologists, clinicians and scientists met to address unsolved issues in transplantation and adapt the Banff schema for renal allograft rejection in response to emerging data and technologies. The outcome of the consensus discussions on renal pathology is provided in this article. Major updates from the 2007 Banff Conference were: inclusion of peritubular capillaritis grading, C4d scoring, interpretation of C4d deposition without morphological evidence of active rejection, application of the Banff criteria to zero-time and protocol biopsies and introduction of a new scoring for total interstitial inflammation (ti-score). In addition, emerging research data led to the establishment of collaborative working groups addressing issues like isolated 'v' lesion and incorporation of omics-technologies, paving the way for future combination of graft biopsy and molecular parameters within the Banff process.

Dysregulated expression of microRNAs (miRNAs) in various tissues has been associated with a variety of diseases, including cancers. Here we demonstrate that miRNAs are present in the serum and plasma of humans and other animals such as mice, rats, bovine fetuses, calves, and horses. The levels of miRNAs in serum are stable, reproducible, and consistent among individuals of the same species. Employing Solexa, we sequenced all serum miRNAs of healthy Chinese subjects and found over 100 and 91 serum miRNAs in male and female subjects, respectively. We also identified specific expression patterns of serum miRNAs for lung cancer, colorectal cancer, and diabetes, providing evidence that serum miRNAs contain fingerprints for various diseases. Two non-small cell lung cancer-specific serum miRNAs obtained by Solexa were further validated in an independent trial of 75 healthy donors and 152 cancer patients, using quantitative reverse transcription polymerase chain reaction assays. Through these analyses, we conclude that serum miRNAs can serve as potential biomarkers for the detection of various cancers and other diseases.

\n Improved approaches for the detection of common epithelial malignancies are urgently needed to reduce the worldwide morbidity and mortality caused by cancer. MicroRNAs (miRNAs) are small (≈22 nt) regulatory RNAs that are frequently dysregulated in cancer and have shown promise as tissue-based markers for cancer classification and prognostication. We show here that miRNAs are present in human plasma in a remarkably stable form that is protected from endogenous RNase activity. miRNAs originating from human prostate cancer xenografts enter the circulation, are readily measured in plasma, and can robustly distinguish xenografted mice from controls. This concept extends to cancer in humans, where serum levels of\n miR-141\n (a miRNA expressed in prostate cancer) can distinguish patients with prostate cancer from healthy controls. Our results establish the measurement of tumor-derived miRNAs in serum or plasma as an important approach for the blood-based detection of human cancer.\n

As in several body fluids, urine is a rich reservoir of extracellular vesicles (EVs) directly originating from cells facing the urinary lumen, including differentiated tubular cells, progenitor cells and infiltrating inflammatory cells. Several markers of glomerular and tubular damage, such as WT-1, ATF3 and NGAL, as well as of renal regeneration, such as CD133, have been identified representing an incredible source of information for diagnostic purposes. In addition, urinary extracellular vesicles (uEVs) appear to be involved in the cell-to-cell communication along the nephron, although this aspect needs further elucidation. Finally, uEVs emerge as potential amplifying or limiting factors in renal damage. Vesicles from injured cells may favour fibrosis and disease progression whereas those from cells with regenerative potential appear to promote cell survival. Here, we will discuss the most recent findings of the literature, on the light of the role of EVs in diagnosis and therapy for damage and repair of the renal tissue.

Extracellular vesicles have been isolated in various body fluids, including urine. The cargo of urinary extracellular vesicles (uEVs) is composed of proteins and nucleic acids reflecting the physiological and possibly pathophysiological state of cells lining the nephron. Because urine is a noninvasive and readily available biofluid, the discovery of uEVs has opened a new field of biomarker research. Their potential use as diagnostic, prognostic, or therapeutic biomarkers for various kidney diseases, including glomerulonephritis, acute kidney injury, tubular disorders, and polycystic kidney disease, is currently being explored. Some challenges, however, remain. These challenges include the need to standardize isolation methods, normalization between samples, and validation of candidate biomarkers. Also, the development of a high-throughput platform to isolate and analyze uEVs, for example, an enzyme-linked immunosorbent assay, is desirable. Here, we review recent studies on uEVs dealing with kidney physiology and pathophysiology. Furthermore, we discuss new and exciting developments regarding vesicles, including their role in cell-to-cell communication and the possibility of using vesicles as a therapy for kidney disorders.

In multicellular organisms, effective communication between cells is a crucial part of cellular and tissue homeostasis. This communication mainly involves direct cell-cell contact as well as the secretion of molecules that bind to receptors at the recipient cells. However, a more recently characterized mode of intercellular communication-the release of membrane vesicles known as exosomes-has been the subject of increasing interest and intensive research over the past decade. Following the discovery of the exosome-mediated immune activation, the pathophysiological roles of exosomes have been recognized in different diseases, including cancer. In this review, we describe the biogenesis and main physical characteristics that define exosomes as a specific population of secreted vesicles, with a special focus on their role in oncogenic transformation and cancer progression.

Prolactinoma is a common subtype of pituitary tumors. Dopamine receptor agonists are the preferred treatment for prolactinoma; however, with this therapy, drug resistance often occurs. In our previous work, we found that partial resistant prolactinomas showed increased fibrosis and that the transforming growth factor (TGF)-β1/Smad3 signaling pathway mediated fibrosis and was involved in drug resistance. Additionally, the success of surgery is known to be heavily influenced by the consistency of the pituitary adenoma. Therefore, in this study, we aimed to clarify the mechanisms of fibrosis in prolactinoma. Using high-throughput sequencing for analysis of microRNAs, we found that miR-93-5p was significantly upregulated in prolactinoma samples with a high degree of fibrosis compared with that in samples without fibrosis. Furthermore, we found that miR-93-5p was negatively correlated with the relative expression of Smad7 and positively correlated with the relative expression of TGF-β1 in clinical prolactinoma samples. In addition, luciferase reporter assays showed that miR-93-5p could downregulate the Smad7 gene, an important inhibitor of the TGF-β1/Smad3 signaling pathway, and activate TGF-β1/Smad3 signaling-mediated fibrosis in a feed-forward loop. Moreover, miR-93-5p could enhance the drug resistance of prolactinoma cells by regulation of TGF-β1/Smad3-dependent fibrosis. Taken together, our findings demonstrated that miR-93-5p may be a potential therapeutic target for inhibiting fibrosis and reducing drug resistance in prolactinoma cells.Copyright © 2019 Elsevier Inc. All rights reserved.

Systemic lupus erythematosus (SLE) is characterized by alternating periods of activity and remission. A portion of the patients suffers from the chronically active form of the disease. The search for clinically useful markers of its activity is ongoing. At present, it is suggested that β2-microglobulin (β2M) may be useful in assessing SLE activity.The objective of the paper was to investigate the relationship between serum β2M concentration and SLE activity.The study group consisted of 69 SLE patients (62 women and 7 men), aged 34.5 ±11 years (19-69). Patients with kidney failure and infection were excluded from the study group. The concentration of β2M was measured using an ELISA test. SLE activity was assessed with Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K), and by measuring the levels of C3 and C4 complement components, anti-double stranded DNA antibodies (anti-dsDNA antibodies) and β2M. The relationship between β2M and the clinical manifestation of SLE was also covered in the study.The study revealed a statistically significant correlation between β2M concentration and SLEDAI-2K disease activity index (p < 0.05; r = 0.6), anti-dsDNA titer (p < 0.05; r = 0.3), and C4 component serum level (p < 0.05; r = -0.3). β2M concentration was significantly higher in patients with arthritis and/or myositis (p = 0.005), vasculitis (p = 0.005), and hematological manifestations of SLE (p = 0.02).Periodical determination of β2M concentration in SLE patients may prove helpful in assessing the disease activity.