scholarly journals The critical role of Krüppel-like factors in kidney disease

2017 ◽  
Vol 312 (2) ◽  
pp. F259-F265 ◽  
Author(s):  
Sandeep K. Mallipattu ◽  
Chelsea C. Estrada ◽  
John C. He
Keyword(s):  
Current Knowledge ◽  
Critical Role ◽  
Vital Role ◽  
Glomerular Filtration Barrier ◽  
Kidney Fibrosis ◽  
Physiological Processes ◽  
Filtration Barrier ◽  
And Function ◽  
Mammalian Embryonic Development

Krüppel-like factors (KLFs) are a family of zinc-finger transcription factors critical to mammalian embryonic development, regeneration, and human disease. There is emerging evidence that KLFs play a vital role in key physiological processes in the kidney, ranging from maintenance of glomerular filtration barrier to tubulointerstitial inflammation to progression of kidney fibrosis. Seventeen members of the KLF family have been identified, and several have been well characterized in the kidney. Although they may share some overlap in their downstream targets, their structure and function remain distinct. This review highlights our current knowledge of KLFs in the kidney, which includes their pattern of expression and their function in regulating key biological processes. We will also critically examine the currently available literature on KLFs in the kidney and offer some key areas in need of further investigation.

scholarly journals Podocyte endocytosis in the regulation of the glomerular filtration barrier

2015 ◽  
Vol 309 (5) ◽  
pp. F398-F405 ◽  
Author(s):  
Kazunori Inoue ◽  
Shuta Ishibe
Keyword(s):  
Glomerular Filtration ◽  
Critical Role ◽  
Vital Role ◽  
Glomerular Filtration Barrier ◽  
Filtration Barrier ◽  
Endocytic Machinery ◽  
Health And Disease ◽  
Models Of Disease ◽  
Genetic Mouse Models

Severe defects in the glomerular filtration barrier result in nephrotic syndrome, which is characterized by massive proteinuria. The podocyte, a specialized epithelial cell with interdigitating foot processes separated by a slit diaphragm, plays a vital role in regulating the passage of proteins from the capillary lumen to Bowman's space. Recent findings suggest a critical role for endocytosis in podocyte biology as highlighted by genetic mouse models of disease and human genetic mutations that result in the loss of the integrity of the glomerular filtration barrier. In vitro podocyte studies have also unraveled a plethora of constituents that are differentially internalized to maintain homeostasis. These observations provide a framework and impetus for understanding the precise regulation of podocyte endocytic machinery in both health and disease.

The Role of microRNAs Identified in the Amniotic Fluid

MicroRNA ◽  
2019 ◽  
Vol 9 (1) ◽  
pp. 8-16 ◽  
Author(s):  
Fasoulakis Zacharias ◽  
Theodora Marianna ◽  
Tsirkas Ioannis ◽  
Tsirka Theodora ◽  
Kalagasidou Sofia ◽  
...  
Keyword(s):  
Amniotic Fluid ◽  
Fetal Development ◽  
Current Knowledge ◽  
Current Data ◽  
Adverse Outcomes ◽  
Many Body ◽  
Kidney Fibrosis ◽  
Physiological Processes ◽  
Fetal Nutrition

Aim:The study aimed to provide an overall view of current data considering the presence of microRNAs in amniotic fluid.Methods:The available literature in MEDLINE, regarding the role of the amniotic fluid in pregnancy and fetal development, was searched for related articles including terms such as “microRNA”, “Amniotic fluid”, “Adverse outcome” and others.Results:The amniotic fluid has an undoubtedly significant part in fetal nutrition, with a protecting and thermoregulatory role alongside. MicroRNAs have proven to be highly expressed during pregnancy in many body liquids including amniotic fluid and are transferred between cells loaded in exosomes, while they are also implicated in many processes during fetal development and could be potential biomarkers for early prediction of adverse outcomes.Conclusion:Current knowledge reveals that amniotic fluid microRNAs participate in many developmental and physiological processes of pregnancy including proliferation of fibroblasts, fetal development, angiogenesis, cardioprotection, activation of signaling pathways, differentiation and cell motility, while the expression profile of specific microRNAs has a potential prognostic role in the prediction of Down syndrome, congenital hydronephrosis and kidney fibrosis.

Lymphocyte signaling and activation by the CARMA1-BCL10-MALT1 signalosome

2016 ◽  
Vol 397 (12) ◽  
pp. 1315-1333 ◽  
Author(s):  
Isabel Meininger ◽  
Daniel Krappmann
Keyword(s):  
Current Knowledge ◽  
Inflammatory Diseases ◽  
Critical Role ◽  
Antigen Receptor ◽  
Lymphocyte Activation ◽  
Downstream Signaling ◽  
Antigen Receptor Signaling ◽  
Autoimmune And Inflammatory Diseases ◽  
And Function

Abstract The CARMA1-BCL10-MALT1 (CBM) signalosome triggers canonical NF-κB signaling and lymphocyte activation upon antigen-receptor stimulation. Genetic studies in mice and the analysis of human immune pathologies unveiled a critical role of the CBM complex in adaptive immune responses. Great progress has been made in elucidating the fundamental mechanisms that dictate CBM assembly and disassembly. By bridging proximal antigen-receptor signaling to downstream signaling pathways, the CBM complex exerts a crucial scaffolding function. Moreover, the MALT1 subunit confers a unique proteolytic activity that is key for lymphocyte activation. Deregulated ‘chronic’ CBM signaling drives constitutive NF-κB signaling and MALT1 activation, which contribute to the development of autoimmune and inflammatory diseases as well as lymphomagenesis. Thus, the processes that govern CBM activation and function are promising targets for the treatment of immune disorders. Here, we summarize the current knowledge on the functions and mechanisms of CBM signaling in lymphocytes and how CBM deregulations contribute to aberrant signaling in malignant lymphomas.

scholarly journals Bile Acids and Microbiota: Multifaceted and Versatile Regulators of the Liver–Gut Axis

2021 ◽  
Vol 22 (3) ◽  
pp. 1397
Author(s):  
Niklas Grüner ◽  
Jochen Mattner
Keyword(s):  
Bile Acids ◽  
Current Knowledge ◽  
Gut Bacteria ◽  
Intestinal Lumen ◽  
Clostridioides Difficile ◽  
Physiological Processes ◽  
Local Site ◽  
Inflammatory Bowel ◽  
And Function

After their synthesis from cholesterol in hepatic tissues, bile acids (BAs) are secreted into the intestinal lumen. Most BAs are subsequently re-absorbed in the terminal ileum and are transported back for recycling to the liver. Some of them, however, reach the colon and change their physicochemical properties upon modification by gut bacteria, and vice versa, BAs also shape the composition and function of the intestinal microbiota. This mutual interplay of both BAs and gut microbiota regulates many physiological processes, including the lipid, carbohydrate and energy metabolism of the host. Emerging evidence also implies an important role of this enterohepatic BA circuit in shaping mucosal colonization resistance as well as local and distant immune responses, tissue physiology and carcinogenesis. Subsequently, disrupted interactions of gut bacteria and BAs are associated with many disorders as diverse as Clostridioides difficile or Salmonella Typhimurium infection, inflammatory bowel disease, type 1 diabetes, asthma, metabolic syndrome, obesity, Parkinson’s disease, schizophrenia and epilepsy. As we cannot address all of these interesting underlying pathophysiologic mechanisms here, we summarize the current knowledge about the physiologic and pathogenic interplay of local site microbiota and the enterohepatic BA metabolism using a few selected examples of liver and gut diseases.

scholarly journals Emerging Roles of Liver Sinusoidal Endothelial Cells in Nonalcoholic Steatohepatitis

Biology ◽  
2020 ◽  
Vol 9 (11) ◽  
pp. 395
Author(s):  
Kunimaro Furuta ◽  
Qianqian Guo ◽  
Petra Hirsova ◽  
Samar H. Ibrahim
Keyword(s):  
Endothelial Cells ◽  
Adhesion Molecules ◽  
Nonalcoholic Steatohepatitis ◽  
Current Knowledge ◽  
Critical Role ◽  
Public Health Problem ◽  
Liver Sinusoidal Endothelial Cells ◽  
Sinusoidal Endothelial Cells ◽  
And Function

Nonalcoholic steatohepatitis (NASH) has become a growing public health problem worldwide, yet its pathophysiology remains unclear. Liver sinusoidal endothelial cells (LSEC) have unique morphology and function, and play a critical role in liver homeostasis. Emerging literature implicates LSEC in many pathological processes in the liver, including metabolic dysregulation, inflammation, angiogenesis, and carcinogenesis. In this review, we highlight the current knowledge of the role of LSEC in each of the progressive phases of NASH pathophysiology (steatosis, inflammation, fibrosis, and the development of hepatocellular carcinoma). We discuss processes that have important roles in NASH progression including the detrimental transformation of LSEC called “capillarization”, production of inflammatory and profibrogenic mediators by LSEC as well as LSEC-mediated angiogenesis. The current review has a special emphasis on LSEC adhesion molecules, and their key role in the inflammatory response in NASH. Moreover, we discuss the pathogenic role of extracellular vesicles and their bioactive cargos in liver intercellular communication, inflammation, and fibrosis. Finally, we highlight LSEC-adhesion molecules and derived bioactive product as potential therapeutic targets for human NASH.

scholarly journals A New Pathogenesis of Albuminuria: Role of Transcytosis

2018 ◽  
Vol 47 (3) ◽  
pp. 1274-1286 ◽  
Author(s):  
Fang-Fang He ◽  
Yi Gong ◽  
Zhen-Qiong Li ◽  
Liang Wu ◽  
Hua-Jun Jiang ◽  
...  
Keyword(s):  
Intracellular Transport ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Vital Role ◽  
Filtration Barrier ◽  
Proximal Tubular ◽  
Pass Through ◽  
And Function ◽  
Multicellular Organisms

Transcytosis is an important intracellular transport process by which multicellular organisms selectively move cargoes from apical to basolateral membranes without disrupting cellular homeostasis. In kidney, macromolecular components in the serum, such as albumin, low-density lipoprotein and immunoglobulins, pass through the glomerular filtration barrier (GFB) and proximal tubular cells (PTCs) by transcytosis. Protein transcytosis plays a vital role in the pathology of albuminuria, which causes progressive destruction of the GFB structure and function. However, the pathophysiological consequences of protein transcytosis in the kidney remain largely unknown. This article summarizes recent researches on the regulation of albumin transcytosis across the GFB and PTCs in both physiological and pathological conditions. Understanding the mechanism of albumin transcytosis may reveal potential therapeutic targets for prevention or alleviation of the pathological consequences of albuminuria.

The Oxford Handbook of the Auditory Brainstem

2018 ◽  
Keyword(s):  
Current Knowledge ◽  
Auditory Pathway ◽  
Auditory Brainstem ◽  
Auditory Midbrain ◽  
Current State ◽  
Neuronal Mechanisms ◽  
Maladaptive Plasticity ◽  
And Function ◽  
Auditory Field

The Oxford Handbook of the Auditory Brainstem provides an in-depth reference to the organization and function of ascending and descending auditory pathways in the mammalian brainstem. Individual chapters are organized along the auditory pathway, beginning with the cochlea and ending with the auditory midbrain. Each chapter provides an introduction to the respective area and summarizes our current knowledge before discussing the disputes and challenges that the field currently faces.The handbook emphasizes the numerous forms of plasticity that are increasingly observed in many areas of the auditory brainstem. Several chapters focus on neuronal modulation of function and plasticity on the synaptic, neuronal, and circuit level, especially during development, aging, and following peripheral hearing loss. In addition, the book addresses the role of trauma-induced maladaptive plasticity with respect to its contribution in generating central hearing dysfunction, such as hyperacusis and tinnitus.The book is intended for students and postdoctoral fellows starting in the auditory field and for researchers of related fields who wish to get an authoritative and up-to-date summary of the current state of auditory brainstem research. For clinical practitioners in audiology, otolaryngology, and neurology, the book is a valuable resource of information about the neuronal mechanisms that are currently discussed as major candidates for the generation of central hearing dysfunction.

scholarly journals Antioxidant and Signaling Role of Plastid-Derived Isoprenoid Quinones and Chromanols

2021 ◽  
Vol 22 (6) ◽  
pp. 2950
Author(s):  
Beatrycze Nowicka ◽  
Agnieszka Trela-Makowej ◽  
Dariusz Latowski ◽  
Kazimierz Strzalka ◽  
Renata Szymańska
Keyword(s):  
Current Knowledge ◽  
Stress Factors ◽  
Oxygenic Photosynthesis ◽  
Ros Generation ◽  
Main Site ◽  
Storage Lipids ◽  
Abiotic Stress Factors ◽  
Cell Components ◽  
And Function

Plant prenyllipids, especially isoprenoid chromanols and quinols, are very efficient low-molecular-weight lipophilic antioxidants, protecting membranes and storage lipids from reactive oxygen species (ROS). ROS are byproducts of aerobic metabolism that can damage cell components, they are also known to play a role in signaling. Plants are particularly prone to oxidative damage because oxygenic photosynthesis results in O2 formation in their green tissues. In addition, the photosynthetic electron transfer chain is an important source of ROS. Therefore, chloroplasts are the main site of ROS generation in plant cells during the light reactions of photosynthesis, and plastidic antioxidants are crucial to prevent oxidative stress, which occurs when plants are exposed to various types of stress factors, both biotic and abiotic. The increase in antioxidant content during stress acclimation is a common phenomenon. In the present review, we describe the mechanisms of ROS (singlet oxygen, superoxide, hydrogen peroxide and hydroxyl radical) production in chloroplasts in general and during exposure to abiotic stress factors, such as high light, low temperature, drought and salinity. We highlight the dual role of their presence: negative (i.e., lipid peroxidation, pigment and protein oxidation) and positive (i.e., contribution in redox-based physiological processes). Then we provide a summary of current knowledge concerning plastidic prenyllipid antioxidants belonging to isoprenoid chromanols and quinols, as well as their structure, occurrence, biosynthesis and function both in ROS detoxification and signaling.

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