Pharmacology, Toxicology and Environmental Health Commons^™

Lipocalin 2 Induces Neuroinflammation And Blood-Brain Barrier Dysfunction Through Liver-Brain Axis In Murine Model Of Nonalcoholic Steatohepatitis, Ayan Mondal, Dipro Bose, Punnag Saha, Sutapa Sarkar, Ratanesh K. Seth, Diana Kimono, Muayad Albadrani, Mitzi Nagarkatti, Prakash Nagarkatti, Saurabh Chatterjee

Faculty Publications

BACKGROUND:

Recent clinical and basic research implicated a strong correlation between NAFLD/NASH phenotypes with ectopic manifestations including neuroinflammation and neurodegeneration, but the mediators and critical pathways involved are not well understood. Lipocalin 2 (Lcn2) is one of the important mediators exclusively produced in the liver and circulation during NASH pathology.

METHODS:

Using murine model of NASH, we studied the role of Lcn2 as a potent mediator of neuroinflammation and neurodegeneration in NASH pathology via the liver-brain axis. RESULTS: Results showed that high circulatory Lcn2 activated 24p3R (Lipocalin2 receptor) in the brain and induced the release of high mobility group box …

A Letter To Reconsider The Conditions For Testing Decontaminated N95 Respirators For Emergency Reuse To Address Shortage, Eric P. Vejerano, Jeonghyeon Ahn

Faculty Publications

The battle with COVID-19 pandemic has resulted in the shortage of personal protective equipment, particularly, N95 respirators. Healthcare workers who reused N95 respirators may resort to unproven methods of cleaning/sterilization that can severely compromise the respirators’ filtration efficiency. A recently issued guideline will test decontaminated N95 respirators against particles with a median diameter of 0.075 ± 0.020 µm at a flow rate of 85 L min–1. For emergency reuse, these conditions may be too stringent. N95 respirators tested at this flow rate had predicted efficiencies of < 69%, assuming complete degradation of their electrostatic coating. Experimental efficiencies were ~15% lower. For emergency reuse, we recommend to either adjust the flow rate closer to normal breathing, or the size of the test particle should reflect that of virus-laden respiratory aerosols (~> 0.5 µm). By reconsidering the test conditions, a substantial fraction of used/decontaminated respirators can …

Using A 3d In Vitro Ovarian Tissue Culture Model To Screen For The Female Reproductive Toxicity Of Pharmaceutical Compounds, Jingshan Xu

Theses and Dissertations

Ovarian toxicity (ovotoxicity) is one of the major side effects of pharmaceutical compounds for women at or before reproductive age. The current gold standard for screening of compounds for ovotoxicity largely relies on preclinical investigations using whole animals. However, in vivo models are time-consuming, costly, and harmful to animals. Here, we developed a three-tiered ovotoxicity screening approach starting from encapsulated in vitro follicle growth (eIVFG) and screened for the potential ovotoxicity of 8 preclinical compounds from AstraZeneca (AZ). Results from Tier 1 and 2 screenings using eIVFG showed that the first 7 tested AZ compounds, AZ-A, -B, -C, -D, -E, …

Mechanistic Insight On Vibrio Gazogenes Mediated Intervention Of Aflatoxin Biosynthesis In Aspergillus Flavus, Rubaiya Jesmin

Theses and Dissertations

Aflatoxin is a liver carcinogen, mycotoxin, and a secondary metabolite that is produced by some plant pathogens within the genus Aspergillus when they infect crops such as corn, peanuts, and cotton. Given the significant adverse health and economic impacts of aflatoxin and a predicted rise of crop contamination with mycotoxins caused by a changing climate, there is a pressing need for exploring new aflatoxin mitigation methods. Previous studies in our laboratory have shown that metabolites from Vibrio gazogenes, an estuarine non-pathogenic bacterium, can inhibit aflatoxin synthesis. However, a direct interaction study between V. gazogenes and aflatoxin producing strains has …

Understanding The Influence Of Changing Climate On Mycotoxin Contamination Of Food And Indoor Fungi-Mediated Respiratory Illness, Mayomi Helen Omebeyinje

Theses and Dissertations

Over the years, climate change has been a major core issue in public and environmental health. The World Health Organization (WHO) estimated that about 250,000 additional death per year would be attributed to climate change between 2030 and 2050 if this situation persists. Since our population depends on (but not limited to) the availability of clean water, good air quality, and exposure to environmental hazards/pathogens, the overall health impact caused by climate change is likely to be overwhelming in the nearest future. This dissertation explored the influence of climate change on fungi diseases and pathogenesis after severe weather conditions (hurricanes …

Temporal Differences In The Emission And Atmospheric Dispersion Of Particulate Matter From Waste And Drinking Water Treatment Facilities, Abdulmalik Alsaif

Theses and Dissertations

Many countries encounter a growing shortage of water, and the reuse of treated or untreated wastewater is their main source. Wastewater Treatment Plants (WWTPs) are mainly designed to remove organic nutrients, large solids, and chemical substances. There are some possible issues regarding WWTPs that are close to residential areas around the world. One of the environmental effects from WWTP that might cause air pollution would be the emission of toxic chemical gases and microorganisms via aerosols that transport bacteria as well as viruses and fungal spores which can be harmful to human health. Therefore, particulate matters (PM) and metrological parameters …

Computational Tools For Analyzing Correlations Between Microbial Biological Diversity And Ecosystems, Behzad Torkian

Theses and Dissertations

Metagenomics has developed into a reliable mechanism to analyze microbial diversity of microbial communities in the recent years. Through the use of next-generation sequencing, metagenomic studies can generate billions of short sequencing reads that are processed by computational tools. However, with the rapid adoption of metagenomics, a large amount of data has been produced. This high level of data production requires the development of computational tools and pipelines to manage data scalability and performance. In this thesis, we developed several tools that will aid in the exploration of the large amount of DNA sequence data, and we further developed a …

Bacterial Water Quality Monitoring As Citizen Science In Congaree National Park, South Carolina, Shea Mccarthy

Theses and Dissertations

Congaree National Park aims to preserve its natural and cultural resources while protecting these benefits for current and future enjoyment. Hydrologic features make up a large portion of the park and attract visitor recreation. There are several known sources of pollution that enter these waterways, mainly from upstream sources of waste discharge. The national park and its surrounding areas hold great ecological significance, however, there are many threats to the surface water quality in this area. Water quality degradation can impact the ecosystem, wildlife, and visitor experience. This project specifically considers exposure to fecal contamination in surface waters from upstream …

The Use Of Polymer-Coated Magnetic Nanoparticles For Amelioration Oil Toxicity And Enhancement Microbial Remediation, Amjed Alabresm

Theses and Dissertations

Oil spills from different sources such as natural seeps, waste waters, runoffs and accidental oil spills can have serious effects on the environment while also resulting in potentially major economic damage. Due to the harmful effects of crude oil components on ecosystems, a rapid response to sequestrate oil is required to minimize any resulting environmental impact. Currently used oil removal methods, in addition to their advantages, also have severe limitations. New techniques have been developed including nanotechnology to address these limitations. A new type of nanoparticle (NP), composed of polyvinylpyrrolidone (PVP) coated iron oxide (magnetite), has been successfully used to …

Development, Validation, And Application Of A Novel Method To Separate And Quantify Silver Intracellular Uptake In Pseudomonas Aeruginosa, Mohammed A. Othman

Theses and Dissertations

Silver nanoparticles (AgNPs) have attracted tremendous attention as a potential broadspectrum antimicrobial agent to overcome multidrug resistant (MDR) infections. However, a comprehensive understanding to AgNPs bactericidal mechanism of action and the relative role of particulate versus ionic Ag in AgNPs antibacterial activity is lacking but essential for their optimization for potential medical applications. Therefore, a novel method to separate and quantify Ag internalization in P. aeruginosa was developed and validated through multimethod approach. The methods used were optical density at 600 nm (OD600), LIVE/DEAD staining, transmission electron microscopy (TEM), and sorbed Ag liberation assays. After optimizing the method, it was …

Microbiome Targeted Therapies In Gulf War Illness, Diana Agnes Kimono

Theses and Dissertations

Gulf war illness (GWI) is a chronic multisymptomatic disorder affecting about 30% of veterans of the 1990-1991 Persian Gulf war. Affected veterans complain of chronic symptoms which begun during or shortly after the war and persist 30 years later. This dissertation is a report of three studies which use a murine model to investigate the microbiome as a therapeutic target in GWI. Mice were exposed to pesticides and the prophylactic drug pyridostigmine bromide (PB) and studied these chemical’s impact on the microbiome in both an acute and persistence model of GWI.

The first study looks at the effect of altered …

Host Abundance Correlates With Gulf War Illness Symptom Persistence Via Nlrp3-Mediated Neuroinflammation And Decreased Brain-Derived Neurotrophic Factor, Diana Kimono, Dipro Bose, Ratanesh K. Seth, Ayan Mondal, Punnag Saha, Patricia Janulewicz, Kimberly Sullivan, Stephen Lasley, Ronnie Horner, Nancy Klimas, Saurabh Chatterjee

Faculty Publications

Neurological disorders are commonly reported among veterans who returned from the Gulf war. Veterans who suffer from Gulf War illness (GWI) complain of continued symptom persistence that includes neurological disorders, muscle weakness, headaches, and memory loss, that developed during or shortly after the war. Our recent research showed that chemical exposure associated microbial dysbiosis accompanied by a leaky gut connected the pathologies in the intestine, liver, and brain. However, the mechanisms that caused the symptoms to persist even 30 years after the war remained elusive to investigators. In this study, we used a rodent model of GWI to investigate the …

Gut Dna Virome Diversity And Its Association With Host Bacteria Regulate Inflammatory Phenotype And Neuronal Immunotoxicity In Experimental Gulf War Illness, Ratanesh K. Seth, Rabia Maqsood, Ayan Mondal, Dipro Bose, Diana Kimono, Larinda A. Holland, Patricia Janulewicz Lloyd, Nancy Klimas, Ronnie Horner, Kimberly Sullivan, Efrem S. Lim, Saurabh Chatterjee

Faculty Publications

Gulf War illness (GWI) is characterized by the persistence of inflammatory bowel disease, chronic fatigue, neuroinflammation, headache, cognitive impairment, and other medically unexplained conditions. Results using a murine model show that enteric viral populations especially bacteriophages were altered in GWI. The increased viral richness and alpha diversity correlated positively with gut bacterial dysbiosis and proinflammatory cytokines. Altered virome signature in GWI mice also had a concomitant weakening of intestinal epithelial tight junctions with a significant increase in Claudin-2 protein expression and decrease in ZO1 and Occludin mRNA expression. The altered virome signature in GWI, decreased tight junction protein level was …

Dysbiosis-Associated Enteric Glial Cell Immune-Activation And Redox Imbalance Modulate Tight Junction Protein Expression In Gulf War Illness Pathology, Diana Kimono, Sutapa Sarkar, Muayad Albadrani, Ratanesh K. Seth, Dipro Bose, Ayan Mondal, Yuxi Li, Amar N. Kar, Mitzi Nagarkatti, Prakash Nagarkatti, Kimberly Sullivan, Patricia Janulewicz, Stephen Lasley, Ronnie Horner, Nancy Klimas, Saurabh Chatterjee

Faculty Publications

About 14% of veterans who suffer from Gulf war illness (GWI) complain of some form of gastrointestinal disorder but with no significant markers of clinical pathology. Our previous studies have shown that exposure to GW chemicals resulted in altered microbiome which was associated with damage associated molecular pattern (DAMP) release followed by neuro and gastrointestinal inflammation with loss of gut barrier integrity. Enteric glial cells (EGC) are emerging as important regulators of the gastrointestinal tract and have been observed to change to a reactive phenotype in several functional gastrointestinal disorders such as IBS and IBD. This study is aimed at …

The Gut-Microbiome In Gulf War Veterans: A Preliminary Report, Patricia A. Janulewicz, Ratanesh K. Seth, Jeffrey M. Carlson, Joy Ajama, Emily Quinn, Timothy Heeren, Nancy Klimas, Steven M. Lasley, Ronnie Horner, Kimberly Sullivan, Saurabh Chatterjee

Faculty Publications

Gulf War Illness (GWI) is a chronic multi-symptom disorder affecting the central nervous system (CNS), immune and gastrointestinal (GI) systems of Gulf War veterans (GWV). We assessed the relationships between GWI, GI symptoms, gut microbiome and inflammatory markers in GWV from the Boston Gulf War Illness Consortium (GWIC). Three groups of GWIC veterans were recruited in this pilot study; GWV without GWI and no gastrointestinal symptoms (controls), GWV with GWI and no gastrointestinal symptoms (GWI-GI), GWV with GWI who reported gastrointestinal symptoms (GW+GI). Here we report on a subset of the first thirteen stool samples analyzed. Results showed significantly different …

Study Of The Inflammatory And Fibrotic Pathology In The Gut Following Microcystin Exposure Under Conditions Of Non-Alcoholic Fatty Liver Disease., Sutapa Sarkar

Theses and Dissertations

Non-alcoholic fatty liver disease (NAFLD) has become a global pandemic with increased risks of chronic inflammation in obese and elderly population. It has become a major public health concern due to the unavailability of proper therapeutic approaches. NAFLD is a condition of the liver involving wide spectrum of events including accumulation of fat in the liver and inflammation, which can progress to a fibrotic and cirrhotic phenotype, often termed as non-alcoholic steatohepatitis (NASH). In this backdrop, exposure to environmental toxins from harmful algal blooms could prove detrimental to the overweight, obese or elderly population. NAFLD not only affects the liver …

Revisiting The Standard Soil Test: The Potential Of Macro- And Microbiological Measures To Improve Agricultural Health And Productivity, Gabriel Jacob Kenne

Theses and Dissertations

The agricultural ecosystem has become the largest non-ice-covered terrestrial ecosystem on the planet and has significant direct and indirect impacts on the global health of both the environment and humanity. Recent shifts in modern agriculture are beginning to focus on the health of soil versus a focus traditionally on crop health and yield at any cost. By managing farmland regeneratively, systems are able to reverse many of the problems created by conventional land management such as erosion and unwanted nutrient runoff, and simultaneously create opportunities to move C from the atmosphere back into the soil. While the ways in which …

Microcystin Exposure And Liver Injury Outcomes In Nafld, Muayad Albadrani

Theses and Dissertations

Non-alcoholic fatty liver disease (NAFLD) is an emerging worldwide pandemic which is highly prevalent among obese individuals including children and adults. In a NAFLD condition, exposure to environmental contaminants or toxins can act as a second/ multiple hit, which leads to the progression of simple steatosis to NASH and ultimately may result in liver cirrhosis. With climate change today, elevated levels of microcystins are an emerging problem in fresh water bodies, which are a source of drinking water. Individuals are therefore at risk of exposure to microcystin through consuming contaminated water. In the progression of NAFLD from one clinical stage …

Investigating The Relationship Of Copd, Lung Cancer, And Polycyclic Aromatic Hydrocarbons From Ambient Air Pollution, Daniel John Kilpatrick

Theses and Dissertations

Polycylic aromatic hydrocarbons (PAHs) are a group of chemically-related compounds with a well-established body of evidence of adverse human health impacts. Additionally, there is a growing area of research on the health outcomes following PAH exposure via air pollution, specifically with chronic obstructive pulmonary disorder (COPD) and lung cancer. The purpose of this dissertation was to investigate the strength of associations among PAHs, COPD, and lung cancer from ambient (outdoor) air pollution. The first objective was to determine if there is a potential environmental link among PAHs, COPD, and lung cancer occurrence among nonsmokers using data from the National Health …

The Effects Of Climate Change On The Ecotoxicology Of Contaminants Of Emerging Concern: Flame Retardants, Contemporary Use Pesticides And Pharmaceuticals Personal Care Products On The Estuarine Grass Shrimp, Palaemontes Pugio, Rajaa Nouri Al-Yassein

Theses and Dissertations

Global Climate Change may adversely affect the environment, increasing water temperature and altered salinity which may affect the toxicity of both legacy pollutants and Contaminants of Emerging Concern (CECs). Acute, 96 hour toxicity tests with adult grass shrimp (Palaemonetes pugio) assessed the effects of CECs (Polybrominated Diphenyl Esther (PBDE) – 47, ibuprofen, bifenthrin, triclosan, and bifenthrin/triclosan mixtures) under Standard Conditions (20°C, 20psu) and different Climate Change Conditions (30°C, and/or35psu) In addition, the grass shrimp microbiome (e.g. Vibrio bacteria) were assessed following acute triclosan exposures at the Maximum Exposure Concentration (MECs) and Minimum Inhibitory Concentration (MICs) under standard conditions. …

The Health Implication And Application Of Silver And Iron Oxide Nanoparticles, Sahar Pourhoseini

Theses and Dissertations

Nanoscience and nanotechnology have successfully created different nanomaterials, which are defined as materials with at least one dimension between 1-100 nm. This small size gives nanomaterials unique and novel properties compared with bulk material, such as a high surface area, specific mechanical, optical and magnetic properties. These novel properties have stimulated the interest of using nanoparticles in a wide range of consumer products and applications including biomedical, pharmaceutical and drug delivery. Silver and iron oxide nanoparticles attracted more attention commercially due to their antibacterial and magnetic properties, respectively. So, the overall objective of this dissertation was: 1) to examine the …

Environmental Microcystin Targets The Microbiome And Increases The Risk Of Intestinal Inflammatory Pathology Via Nox2 In Underlying Murine Model Of Nonalcoholic Fatty Liver Disease, Sutapa Sarkar, Diana Kimono, Muayad Albadrani, Ratanesh K. Seth, Philip Busbee, Hasan Alghetaa, Dwayne E. Porter, Geoff I. Scott, Bryan Brooks, Mitzi Nagarkatti, Prakash Nagarkatti, Saurabh Chatterjee

Faculty Publications

With increased climate change pressures likely to influence harmful algal blooms, exposure to microcystin, a known hepatotoxin and a byproduct of cyanobacterial blooms can be a risk factor for NAFLD associated comorbidities. Using both in vivo and in vitro experiments we show that microcystin exposure in NAFLD mice cause rapid alteration of gut microbiome, rise in bacterial genus known for mediating gut inflammation and lactate production. Changes in the microbiome were strongly associated with inflammatory pathology in the intestine, gut leaching, tight junction protein alterations and increased oxidative tyrosyl radicals. Increased lactate producing bacteria from the altered microbiome was associated …

A Site Characterization And Assessment Of The Bushy Park Reservoir, A Charleston-Area Drinking Water Source, And Its Surrounding Watersheds In Response To Community Concerns, Bradley Joseph Chandler

Theses and Dissertations

Access to clean, safe drinking water is considered a basic human right (WHO 2004). It is vital to maintain adequate monitoring of source waters as well as to investigate claims of degraded source waters. In June of 2017, inaccurate reporting led many community members in Mt. Pleasant, SC to believe that their drinking water might be tainted, leading to elevated cases of brain cancer in children. Though steps were taken to test and ensure the drinking water was safe, fear over the health of the city’s drinking water still persists. This is largely due to the involvement of famed water …

Relative Importance Of Ions And Particles In Silver Nanoparticle Uptake And Accumulation In Keystone Estuarine Organisms; Prorocentrum Minimum And Crassostrea Virginica, Shelby Victoria Butz

Theses and Dissertations

In marine systems, silver is regarded as being one of the most toxic and readily accumulated metals, and is known to be taken up and accumulate within marine invertebrates, fish, phytoplankton and seaweeds. Reported open ocean concentrations of silver range from 0.1 – 2 ng L-1 while silver concentrations in coastal waters are typically 5 to 10 times higher than open ocean values (0.1 - 50 ng L-1). The determination of silver in marine and coastal waters presents several challenges including low concentrations and matrix complexity of seawater, which creates interferences and other challenges for many instrumental techniques creating a …

Nutrient Limitation Of Phytoplankton In Lake Wateree, South Carolina: Implications For Future Water Quality Management, Kara M. Clyburn

Theses and Dissertations

Cultural eutrophication is a primary contributor to phytoplankton production in freshwater lakes from excess anthropogenic nutrient inputs, and resulting impacts on water quality, aquatic ecosystems, human and animal health are increasing worldwide. Understanding the factors that limit phytoplankton growth is an important strategy for identifying and managing nutrient sources and successfully controlling the over- enrichment of nitrogen (N) and/or phosphorus (P) in freshwater lakes. The Redfield molecular ratio of carbon (C), N and P maintains that the C:N:P molar ratio is 106:16:1 when nutrients are not limiting, and the ecosystem is balanced. A N:P molar ratio > 20:1 tends to be …

Resveratrol Attenuates Allergic Asthma And Associated Inflammation In The Lungs Through Regulation Of Mirna-34a That Targets Foxp3 In Mice, Esraah Alharris, Hasan Alghetaa, Ratanesh K. Seth, Saurabh Chatterjee, Narendra P. Singh, Mitzi Nagarkatti, Prakash Nagarkatti

Faculty Publications

Asthma is a chronic inflammatory disease of airways mediated by T-helper 2 (Th2) cells involving complex signaling pathways. Although resveratrol has previously been shown to attenuate allergic asthma, the role of miRNA in this process has not been studied. We investigated the effect of resveratrol on ovalbumin-induced experimental allergic asthma in mice. To that end, BALB/c mice were immunized with ovalbumin (OVA) intraperitoneally followed by oral gavage of vehicle (OVA-veh) or resveratrol (100 mg/kg body) (OVA-res). On day 7, the experimental groups received intranasal challenge of OVA followed by 7 days of additional oral gavage of vehicle or resveratrol. At …

Macromolecular-Clustered Facial Amphiphilic Antimicrobials, Md Anisur Rahman, Marpe Bam, Edgar Luat, Moumita Sharmin Jui, Mitra S. Ganewatta, Tinom Shokfai, Mitzi Nagarkatti, Alan W. Decho

Faculty Publications

Bacterial infections and antibiotic resistance, particularly by Gram-negative pathogens, have become a global healthcare crisis. We report the design of a class of cationic antimicrobial polymers that cluster local facial amphiphilicity from repeating units to enhance interactions with bacterial membranes without requiring a globally conformational arrangement associated with highly unfavorable entropic loss. This concept of macromolecular architectures is demonstrated with a series of multicyclic natural product-based cationic polymers. We have shown that cholic acid derivatives with three charged head groups are more potent and selective than lithocholic and deoxycholic counterparts, particularly against Gram-negative bacteria. This is ascribed to the formation …

Influenza Virus Infectivity Is Retained In Aerosols And Droplets Independent Of Relative Humidity, Karen A. Kormuth, Kaisen Lin, Aaron J. Prussin, Eric P. Vejerano, Andrea J. Tiwari, Steve S. Cox, Micheal M. Myerburg, Seema S. Lakdawala, Linsey C. Marr

Faculty Publications

Pandemic and seasonal influenza viruses can be transmitted through aerosols and droplets, in which viruses must remain stable and infectious across a wide range of environmental conditions. Using humidity-controlled chambers, we studied the impact of relative humidity on the stability of 2009 pandemic influenza A(H1N1) virus in suspended aerosols and stationary droplets. Contrary to the prevailing paradigm that humidity modulates the stability of respiratory viruses in aerosols, we found that viruses supplemented with material from the apical surface of differentiated primary human airway epithelial cells remained equally infectious for 1 hour at all relative humidities tested. This sustained infectivity was …

Aerosol Microdroplets Exhibit A Stable Ph Gradient, Haoran Wei, Eric P. Vejerano, Weinan Leng, Qishen Haung, Marjorie R. Willner, Linsey C. Marr, Peter J. Vikesland

Faculty Publications

Suspended aqueous aerosol droplets (<50 μm) are microreactors for many important atmospheric reactions. In droplets and other aquatic environments, pH is arguably the key parameter dictating chemical and biological processes. The nature of the droplet air/ water interface has the potential to significantly alter droplet pH relative to bulk water. Historically, it has been challenging to measure the pH of individual droplets because of their inaccessibility to conventional pH probes. In this study, we scanned droplets containing 4-mercaptobenzoic acid–functionalized gold nanoparticle pH nanoprobes by 2D and 3D laser confocal Raman microscopy. Using surface-enhanced Raman scattering, we acquired the pH distribution inside approximately 20-μm-diameter phosphate-buffered aerosol droplets and found that the pH in the core of a droplet is higher than that of bulk solution by up to 3.6 pH units. This finding suggests the accumulation of protons at the air/water interface and is consistent with recent thermodynamic model results. The existence of this pH shift was corroborated by the observation that a catalytic reaction that occurs only under basic conditions (i.e., dimerization of 4-aminothiophenol to produce dimercaptoazobenzene) occurs within the high pH core of a droplet, but not in bulk solution. Our nanoparticle probe enables pH quantification through the cross-section of an aerosol droplet, revealing a spatial gradient that has implications for acid-base–catalyzed atmospheric chemistry.

High Circulatory Leptin Mediated Nox-2-Peroxynitrite-Mir21 Axis Activate Mesangial Cells And Promotes Renal Inflammatory Pathology In Nonalcoholic Fatty Liver Disease, Firas Alhasson, Ratanesh K. Seth, Sutapa Sarkar, Diana A. Kimono, Muayad S. Albadrani, Diptadip Dattaroy, Varun Chandrashekaran, Geoffry Scott, Samir Raychoudhury, Mitzi Nagarkatti, Prakash Nagarkatti, Anna Mae Diehl, Saurabh Chatterjee

Faculty Publications

High circulatory insulin and leptin followed by underlying inflammation are often ascribed to the ectopic manifestations in non-alcoholic fatty liver disease (NAFLD) but the exact molecular pathways remain unclear. We have shown previously that CYP2E1-mediated oxidative stress and circulating leptin in NAFLD is associated with renal disease severity. Extending the studies, we hypothesized that high circulatory leptin in NAFLD causes renal mesangial cell activation and tubular inflammation via a NOX2 dependent pathway that upregulates proinflammatory miR21. High-fat diet (60% kcal) was used to induce fatty liver phenotype with parallel insulin and leptin resistance. The kidneys were probed for mesangial cell …