scholarly journals THU0236 URINARY EXOSOMAL MIR-31, MIR-107 AND MIR-135B-5P FROM TUBULAR RENAL CELLS AS RESPONDER BIOMARKER IN LUPUS NEPHRITIS

2019 ◽  
Author(s):  
Cristina Solé-Marcé ◽  
Eloi Garcia-Vives ◽  
Irene Agraz ◽  
Josep Ordi-Ros ◽  
Josefina Cortés-Hernández
Keyword(s):  
Lupus Nephritis ◽  
Renal Cells

scholarly journals The Th17/IL-17 Axis and Kidney Diseases, With Focus on Lupus Nephritis

2021 ◽  
Vol 8 ◽  
Author(s):  
Feliciano Chanana Paquissi ◽  
Hugo Abensur
Keyword(s):  
Lupus Nephritis ◽  
Immune Cells ◽  
Lupus Erythematosus ◽  
Tissue Damage ◽  
Epithelial Mesenchymal Transition ◽  
Kidney Diseases ◽  
Special Focus ◽  
Renal Cells ◽  
Effector Cells ◽  
Mesenchymal Transition

Systemic lupus erythematosus (SLE) is a disease characterized by dysregulation and hyperreactivity of the immune response at various levels, including hyperactivation of effector cell subtypes, autoantibodies production, immune complex formation, and deposition in tissues. The consequences of hyperreactivity to the self are systemic and local inflammation and tissue damage in multiple organs. Lupus nephritis (LN) is one of the most worrying manifestations of SLE, and most patients have this involvement at some point in the course of the disease. Among the effector cells involved, the Th17, a subtype of T helper cells (CD4+), has shown significant hyperactivation and participates in kidney damage and many other organs. Th17 cells have IL-17A and IL-17F as main cytokines with receptors expressed in most renal cells, being involved in the activation of many proinflammatory and profibrotic pathways. The Th17/IL-17 axis promotes and maintains repetitive tissue damage and maladaptive repair; leading to fibrosis, loss of organ architecture and function. In the podocytes, the Th17/IL-17 axis effects include changes of the cytoskeleton with increased motility, decreased expression of health proteins, increased oxidative stress, and activation of the inflammasome and caspases resulting in podocytes apoptosis. In renal tubular epithelial cells, the Th17/IL-17 axis promotes the activation of profibrotic pathways such as increased TGF-β expression and epithelial-mesenchymal transition (EMT) with consequent increase of extracellular matrix proteins. In addition, the IL-17 promotes a proinflammatory environment by stimulating the synthesis of inflammatory cytokines by intrinsic renal cells and immune cells, and the synthesis of growth factors and chemokines, which together result in granulopoiesis/myelopoiesis, and further recruitment of immune cells to the kidney. The purpose of this work is to present the prognostic and immunopathologic role of the Th17/IL-17 axis in Kidney diseases, with a special focus on LN, including its exploration as a potential immunotherapeutic target in this complication.

scholarly journals Autoantibodies and Resident Renal Cells in the Pathogenesis of Lupus Nephritis: Getting to Know the Unknown

2012 ◽  
Vol 2012 ◽  
pp. 1-13 ◽  
Author(s):  
Susan Yung ◽  
Tak Mao Chan
Keyword(s):  
Lupus Nephritis ◽  
Lupus Erythematosus ◽  
Critical Role ◽  
Surface Proteins ◽  
Kidney Cells ◽  
Renal Cells ◽  
Self Tolerance ◽  
Mediators Of Inflammation ◽  
Kidney Involvement ◽  
Dsdna Antibodies

Systemic lupus erythematosus is characterized by a breakdown of self-tolerance and production of autoantibodies. Kidney involvement (i.e., lupus nephritis) is both common and severe and can result in permanent damage within the glomerular, vascular, and tubulo-interstitial compartments of the kidney, leading to acute or chronic renal failure. Accumulating evidence shows that anti-dsDNA antibodies play a critical role in the pathogenesis of lupus nephritis through their binding to cell surface proteins of resident kidney cells, thereby triggering the downstream activation of signaling pathways and the release of mediators of inflammation and fibrosis. This paper describes the mechanisms through which autoantibodies interact with resident renal cells and how this interaction plays a part in disease pathogenesis that ultimately leads to structural and functional alterations in lupus nephritis.

scholarly journals Recent advances in the understanding of renal inflammation and fibrosis in lupus nephritis

F1000Research ◽  
2017 ◽  
Vol 6 ◽  
pp. 874 ◽  
Author(s):  
Susan Yung ◽  
Desmond YH Yap ◽  
Tak Mao Chan
Keyword(s):  
Lupus Nephritis ◽  
Treatment Options ◽  
Critical Role ◽  
Fibrous Tissue ◽  
Kidney Injury ◽  
High Dose ◽  
Renal Cells ◽  
Autoantibody Production ◽  
Recent Advances ◽  
Dsdna Antibody

Lupus nephritis is a potentially reversible cause of severe acute kidney injury and is an important cause of end-stage renal failure in Asians and patients of African or Hispanic descent. It is characterized by aberrant exaggerated innate and adaptive immune responses, autoantibody production and their deposition in the kidney parenchyma, triggering complement activation, activation and proliferation of resident renal cells, and expression of pro-inflammatory and chemotactic molecules leading to the influx of inflammatory cells, all of which culminate in destruction of normal nephrons and their replacement by fibrous tissue. Anti-double-stranded DNA (anti-dsDNA) antibody level correlates with disease activity in most patients. There is evidence that apart from mediating pathogenic processes through the formation of immune complexes, pathogenic anti-dsDNA antibodies can bind to resident renal cells and induce downstream pro-apoptotic, pro-inflammatory, or pro-fibrotic processes or a combination of these. Recent data also highlight the critical role of macrophages in acute and chronic kidney injury. Though clinically effective, current treatments for lupus nephritis encompass non-specific immunosuppression and the anti-inflammatory action of high-dose corticosteroids. The clinical and histological impact of novel biologics targeting pro-inflammatory molecules remains to be investigated. Insight into the underlying mechanisms that induce inflammatory and fibrotic processes in the kidney of lupus nephritis could present opportunities for more specific novel treatment options to improve clinical outcomes while minimizing off-target untoward effects. This review discusses recent advances in the understanding of pathogenic mechanisms leading to inflammation and fibrosis of the kidney in lupus nephritis in the context of established standard-of-care and emerging therapies.

scholarly journals IFN-I Mediates Lupus Nephritis From the Beginning to Renal Fibrosis

2021 ◽  
Vol 12 ◽  
Author(s):  
Xuewei Ding ◽  
Yi Ren ◽  
Xiaojie He
Keyword(s):  
Lupus Nephritis ◽  
Lupus Erythematosus ◽  
Renal Fibrosis ◽  
Type I Interferons ◽  
Type I ◽  
Renal Cells ◽  
Inflammatory Reactions ◽  
Pathological Mechanism ◽  
New Perspective

Lupus nephritis (LN) is a common complication of systemic lupus erythematosus (SLE) and a major risk factor for morbidity and mortality. The abundant cell-free nucleic (DNA/RNA) in SLE patients, especially dsDNA, is a key substance in the pathogenesis of SLE and LN. The deposition of DNA/RNA-immune complexes (DNA/RNA-ICs) in the glomerulus causes a series of inflammatory reactions that lead to resident renal cell disturbance and eventually renal fibrosis. Cell-free DNA/RNA is the most effective inducer of type I interferons (IFN-I). Resident renal cells (rather than infiltrating immune cells) are the main source of IFN-I in the kidney. IFN-I in turn damages resident renal cells. Not only are resident renal cells victims, but also participants in this immunity war. However, the mechanism for generation of IFN-I in resident renal cells and the pathological mechanism of IFN-I promoting renal fibrosis have not been fully elucidated. This paper reviews the latest epidemiology of LN and its development process, discusses the mechanism for generation of IFN-I in resident renal cells and the role of IFN-I in the pathogenesis of LN, and may open a new perspective for the treatment of LN.

scholarly journals MicroRNAs in Lupus Nephritis–Role in Disease Pathogenesis and Clinical Applications

2021 ◽  
Vol 22 (19) ◽  
pp. 10737
Author(s):  
Benjamin Y. F. So ◽  
Desmond Y. H. Yap ◽  
Tak Mao Chan
Keyword(s):  
Lupus Nephritis ◽  
Immune Cells ◽  
Small Rnas ◽  
Clinical Utility ◽  
Clinical Applications ◽  
Renal Cells ◽  
Kidney Fibrosis ◽  
Protein Levels ◽  
Genetic Sequences

MicroRNAs (miRs) are non-coding small RNAs that act as epigenetic modulators to regulate the protein levels of target mRNAs without modifying the genetic sequences. The role of miRs in the pathogenesis of lupus nephritis (LN) is increasingly recognized and highly complex. Altered levels of different miRs are observed in the blood, urine and kidney tissues of murine LN models and LN patients. Accumulating evidence suggests that these miRs can modulate immune cells and various key inflammatory pathways, and their perturbations contribute to the aberrant immune response in LN. The dysregulation of miRs in different resident renal cells and urinary exosomes can also lead to abnormal renal cell proliferation, inflammation and kidney fibrosis in LN. While miRs may hold promise in various clinical applications in LN patients, there are still many potential limitations and safety concerns for their use. Further studies are worthwhile to examine the clinical utility of miRs in the diagnosis, disease activity monitoring, prognostication and treatment of LN.

scholarly journals Mediators of Inflammation and Their Effect on Resident Renal Cells: Implications in Lupus Nephritis

2013 ◽  
Vol 2013 ◽  
pp. 1-10 ◽  
Author(s):  
Susan Yung ◽  
Kwok Fan Cheung ◽  
Qing Zhang ◽  
Tak Mao Chan
Keyword(s):  
Lupus Nephritis ◽  
Lupus Erythematosus ◽  
Mesangial Cells ◽  
Kidney Injury ◽  
Organ Damage ◽  
Type I Interferons ◽  
Type I ◽  
Renal Cells ◽  
Mediators Of Inflammation ◽  
Gene And Protein Expression

Lupus nephritis affects up to 70% of patients with systemic lupus erythematosus and is a major cause of morbidity and mortality. It is characterized by a breakdown of immune tolerance, production of autoantibodies, and deposition of immune complexes within the kidney parenchyma, resulting in local inflammation and subsequent organ damage. To date, numerous mediators of inflammation have been implicated in the development and progression of lupus nephritis, and these include cytokines, chemokines, and glycosaminoglycans. Of these, type I interferons (IFNs) can increase both gene and protein expression of cytokines and chemokines associated with lupus susceptibility, and interleukin-6 (IL-6), tumor necrosis factor-α(TNF-α) and hyaluronan have been shown to elicit both pro- and anti-inflammatory effects on infiltrating and resident renal cells depending on the status of their microenvironment. Expression of IL-6, TNF-α, type I IFNs, and hyaluronan are increased in the kidneys of patients and mice with active lupus nephritis and have been shown to contribute to disease pathogenesis. There is also evidence that despite clinical remission, ongoing inflammatory processes may occur within the glomerular and tubulointerstitial compartments of the kidney, which further promote kidney injury. In this review, we provide an overview of the synthesis and putative roles of IL-6, TNF-α, IFN-α, and hyaluronan in the pathogenesis of lupus nephritis focusing on their effects on human mesangial cells and proximal renal tubular epithelial cells.

Sign in / Sign up

Export Citation Format

Share Document