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 Clinical Applications of Natriuretic Peptides in Assessment of Valvular Heart Disease

2015 ◽  
Vol 2015 ◽  
pp. 1-6 ◽  
Author(s):  
Abhishek Sharma ◽  
Vaseem Ahmed ◽  
Aakash Garg ◽  
Chirag Aggarwal
Keyword(s):  
Heart Disease ◽  
Natriuretic Peptides ◽  
Valvular Heart Disease ◽  
Clinical Utility ◽  
Surgical Intervention ◽  
Clinical Applications ◽  
Asymptomatic Patients ◽  
Routine Surveillance ◽  
Valvular Lesions

Biomarkers such as natriuretic peptides (NPs) have evolving clinical utility beyond the scope of heart failure. The role of NPs in the management of valvular heart disease is a growing area of investigation. NPs have much potential in the assessment of asymptomatic patients with hemodynamically significant valvular lesions who have traditionally been excluded from consideration of surgical intervention. NPs also have a role in the risk stratification of these patients as well as in routine surveillance and monitoring. Together with echocardiographic data and functional status, NPs are being incorporated into the management of valvular heart disease. In this review we examine the evidence for the role of natriuretic peptides in assessment of VHD.

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 The Role of Primary Cilia in Thyroid Cancer: From Basic Research to Clinical Applications

2021 ◽  
Vol 12 ◽  
Author(s):  
Cheng-Xu Ma ◽  
Xiao-Ni Ma ◽  
Ying-Dong Li ◽  
Song-Bo Fu
Keyword(s):  
Clinical Utility ◽  
Primary Cilia ◽  
Therapeutic Strategy ◽  
Therapeutic Response ◽  
Basic Research ◽  
Clinical Applications ◽  
Follicle Cells ◽  
Thyroid Follicle ◽  
Potential Clinical Utility

Primary cilia (PC) are microtubule-based organelles that are present on nearly all thyroid follicle cells and play an important role in physiological development and in maintaining the dynamic homeostasis of thyroid follicles. PC are generally lost in many thyroid cancers (TCs), and this loss has been linked to the malignant transformation of thyrocytes, which is regulated by PC-mediated signaling reciprocity between the stroma and cancer cells. Restoring PC on TC cells is a possible promising therapeutic strategy, and the therapeutic response and prognosis of TC are associated with the presence or absence of PC. This review mainly discusses the role of PC in the normal thyroid and TC as well as their potential clinical utility.

Abstract 175: The Role of Axl in Accumulation of Immune Cells in Kidney and the Onset of Hypertension

Hypertension ◽  
2012 ◽  
Vol 60 (suppl_1) ◽  
Author(s):  
Sri Nagarjun Batchu ◽  
Angie Hughson ◽  
Janice Gerloff ◽  
Deborah J Fowell ◽  
Vyacheslav A Korshunov
Keyword(s):  
Blood Pressure ◽  
Immune Cells ◽  
Immune Cell ◽  
Kidney Injury ◽  
Wild Type ◽  
Protein Levels ◽  
Immune Cell Subsets ◽  
Early Increase ◽  
Salt Hypertension

Introduction: Gas6/Axl pathway contributes to elevation of blood pressure. Immune cells are implicated in initiation and maintenance of hypertension. In this study we aimed to investigate the role of Axl in immune cells on kidney injury and initiation of hypertension. Methods and Results: Deoxycorticosterone-acetate (DOCA; 75mg, 60days release) and salt hypertension was induced for 1wk or 6wks in four groups of Axl chimeras (n=4-5) that were generated by bone marrow (BM) transplant. Multi parameter flow cytometry was used to quantify five major immune cell subsets in digested kidneys from Axl chimeras. Systolic blood pressure (SBP) increased by 30mmHg in Axl+/+ →Axl+/+, Axl-/- →Axl-/- and Axl+/+ →Axl-/- mice after 1wk of DOCA-salt. However, chimeras that lack Axl in the BM cells (Axl-/- →Axl+/+) showed reduction in early increase in SBP (16+2mmHg). We observed a significant decrease in urine protein levels in Axl-/- →Axl+/+ (0.3+0.1μg/μl) compared to other Axl chimeras (∼0.7μg/μl) after 1wk of DOCA-salt. Kidney glomeruli areas were reduced in Axl-/- →Axl+/+ (4,143+229μm 2 ) compared to other Axl chimeras (∼6,000μm 2 ) after 6wks of DOCA-salt. Kidneys from Axl-/- →Axl-/- showed an increase in total leukocytes (8 vs. 4%), B cells (29 vs. 12%) and decrease in monocytes/macrophages (16 vs. 22%) and dendritic cells (5 vs. 10%) compared to Axl+/+ →Axl+/+. Moreover, Axl-/- →Axl+/+ showed further increase in leukocytes (17%), B (39%) and dendritic (13%) cells in kidneys compared to other Axl chimeras. In addition a small percentage of wild type T cells was increased in the kidneys from Axl-/- →Axl+/+ chimeras. Conclusions: These findings suggest that Axl expression in BM-derived cells is critical for kidney injury in DOCA-salt hypertension. Axl-dependent pathways regulate immune cell populations in the kidneys during initiation of hypertension. This study was supported by HL105623 grant (VAK)

Role of immune cells in crystal-induced kidney fibrosis

2018 ◽  
Vol 68-69 ◽  
pp. 280-292 ◽  
Author(s):  
Ermanila Dhana ◽  
Isis Ludwig-Portugall ◽  
Christian Kurts
Keyword(s):  
Immune Cells ◽  
Kidney Fibrosis

Protective role for CCR5 in murine lupus nephritis

2012 ◽  
Vol 302 (11) ◽  
pp. F1503-F1515 ◽  
Author(s):  
Jan-Eric Turner ◽  
Hans-Joachim Paust ◽  
Sabrina B. Bennstein ◽  
Phillip Bramke ◽  
Christian Krebs ◽  
...  
Keyword(s):  
T Cell ◽  
Lupus Nephritis ◽  
Tissue Injury ◽  
Protective Role ◽  
T Cell Response ◽  
T Cell Subsets ◽  
Murine Lupus ◽  
Protein Levels ◽  
Chemokine Receptor Ccr5

Leukocyte infiltration is a characteristic feature of human and experimental lupus nephritis and is closely correlated with loss of renal function. The chemokine receptor CCR5 is expressed on monocyte and T cell subsets and is thought to play an important role in recruiting these cells into inflamed organs. To investigate the functional role of CCR5 in lupus nephritis, CCR5-deficient mice were backcrossed onto the lupus-prone MRL- Faslpr (MRL/lpr) genetic background. Unexpectedly, CCR5−/− MRL/lpr mice developed an aggravated course of lupus nephritis in terms of glomerular tissue injury and albuminuria. Deterioration of the nephritis was associated with an overall increase in mononuclear cell infiltration into the kidney, whereas renal leukocyte subtype balance, systemic T cell response, and autoantibody formation were unaffected by CCR5 deficiency. Renal and systemic protein levels of the CCR5 ligand CCL3, which can also attract leukocytes via its alternate receptor CCR1, were significantly increased in nephritic CCR5−/− MRL/lpr mice. Further studies revealed that the systemic increase in the CCR5/CCR1 ligand is also observed in nonimmune CCR5−/− C57BL/6 mice and that this increase was due to a reduced clearance, rather than an overproduction, of CCL3. Taken together, our data support the hypothesis that CCR5-dependent consumption of its own ligands may act as a negative feedback loop to restrain local chemokine levels within inflamed tissues, thereby limiting inflammatory cell influx.

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.

Staring Down Death

Crisis ◽  
2016 ◽  
Vol 37 (3) ◽  
pp. 212-217 ◽  
Author(s):  
Thomas E. Joiner ◽  
Melanie A. Hom ◽  
Megan L. Rogers ◽  
Carol Chu ◽  
Ian H. Stanley ◽  
...  
Keyword(s):  
Suicide Risk ◽  
Clinical Utility ◽  
Blink Rate ◽  
Specific Task ◽  
Careful Planning ◽  
Eye Blink ◽  
Eye Blinks ◽  
Potential Clinical Utility ◽  
The Relationship

Abstract. Background: Lowered eye blink rate may be a clinically useful indicator of acute, imminent, and severe suicide risk. Diminished eye blink rates are often seen among individuals engaged in heightened concentration on a specific task that requires careful planning and attention. Indeed, overcoming one’s biological instinct for survival through suicide necessitates premeditation and concentration; thus, a diminished eye blink rate may signal imminent suicidality. Aims: This article aims to spur research and clinical inquiry into the role of eye blinks as an indicator of acute suicide risk. Method: Literature relevant to the potential connection between eye blink rate and suicidality was reviewed and synthesized. Results: Anecdotal, cognitive, neurological, and conceptual support for the relationship between decreased blink rate and suicide risk is outlined. Conclusion: Given that eye blinks are a highly observable behavior, the potential clinical utility of using eye blink rate as a marker of suicide risk is immense. Research is warranted to explore the association between eye blink rate and acute suicide risk.

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