Digital Commons Network^™

A Human T-Cell Lymphotropic Virus Type 1 Enhancer Of Myc Transforming Potential Stabilizes Myc-Tip60 Transcriptional Interactions, Soumya Awasthi, Anima Sharma, Kasuen Wong, Junyu Zhang, Elizabeth F. Matlock, Lowery Rogers, Pamela Motloch, Shigeki Takemoto, Hirokuni Taguchi, Michael D. Cole

Dartmouth Scholarship

The human T-cell lymphotropic virus type 1 (HTLV-1) infects and transforms CD4+ lymphocytes and causes adult T-cell leukemia/lymphoma (ATLL), an aggressive lymphoproliferative disease that is often fatal. Here, we demonstrate that the HTLV-1 pX splice-variant p30II markedly enhances the transforming potential of Myc and transcriptionally activates the human cyclin D2 promoter, dependent upon its conserved Myc-responsive E-box enhancer elements, which are associated with increased S-phase entry and multinucleation. Enhancement of c-Myc transforming activity by HTLV-1 p30II is dependent upon the transcriptional coactivators, transforming transcriptional activator protein/p434 and TIP60, and it requires TIP60 histone acetyltransferase (HAT) activity and correlates with the …

Functionally Active T1-T1 Interfaces Revealed By The Accessibility Of Intracellular Thiolate Groups In Kv4 Channels., Guangyu Wang, Mohammad Shahidullah, Carmen A Rocha, Candace Strang, Paul J Pfaffinger, Manuel Covarrubias

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Gating of voltage-dependent K(+) channels involves movements of membrane-spanning regions that control the opening of the pore. Much less is known, however, about the contributions of large intracellular channel domains to the conformational changes that underlie gating. Here, we investigated the functional role of intracellular regions in Kv4 channels by probing relevant cysteines with thiol-specific reagents. We find that reagent application to the intracellular side of inside-out patches results in time-dependent irreversible inhibition of Kv4.1 and Kv4.3 currents. In the absence or presence of Kv4-specific auxiliary subunits, mutational and electrophysiological analyses showed that none of the 14 intracellular cysteines is …

Thymidine-Dependent Staphylococcus Aureus Small-Colony Variants Are Associated With Extensive Alterations In Regulator And Virulence Gene Expression Profiles, Barbara C. Kahl, Gunnar Belling, Petra Becker, Indranil Chatterjee, Katrin Wardecki, Karin Hilgert, Ambrose Cheung

Dartmouth Scholarship

Chronic airway infection is a hallmark of cystic fibrosis (CF) and many CF patients are infected persistently by Staphylococcus aureus. Thymidine-dependent trimethoprim-sulfamethoxazole (SXT)-resistant S. aureus small-colony variants (SCVs), often in combination with isogenic normal S. aureus phenotypes, are highly prevalent and persistent in airway secretions of CF patients due to long-term SXT therapy (B. Kahl, M. Herrmann, A. S. Everding, H. G. Koch, K. Becker, E. Harms, R. A. Proctor, and G.

Diets And Coexistence Of The Sea Urchins Lytechinus Variegatus And Arbacia Punctulata (Echinodermata) Along The Central Florida Gulf Coast, Janessa Cobb, John M. Lawrence

Integrative Biology Faculty and Staff Publications

The basis for coexistence of similar species is fundamental in community ecology. One mechanism for coexistence is differentiation of diets. Lytechinus variegatus and Arbacia punctulata coexist in different microhabitats along the Florida gulf coast. Their great difference in morphology might affect their choice of microhabitats and diet. We analyzed diets of both species at 1 offshore and 1 nearshore site where both occurred in relatively equal numbers, an offshore site dominated by A. punctulata and an offshore site dominated by L. variegatus. Gut contents were analyzed to determine the diet. A. punctulata prim. consumed sessile invertebrates except on dates …

Evaluating Forensic Dna Evidence, Dan E. Krane, William C. Thompson

Biological Sciences Faculty Publications

No abstract provided.

A Critical Role For Kalirin In Ngf Signaling Through Trka, Kausik Chakrabarti, Rong Lin, Noraisha I. Schiller, Yanping Wang, David Koubi, Ying-Xin Fan, Brian B. Rudkin, Gibbes R. Johnson, Martin R. Schiller

Life Sciences Faculty Research

Kalirin is a multidomain guanine nucleotide exchange factor (GEF) that activates Rho proteins, inducing cytoskeletal rearrangement in neurons. Although much is known about the effects of Kalirin on Rho GTPases and neuronal morphology, little is known about the association of Kalirin with the receptor/signaling systems that affect neuronal morphology. Our experiments demonstrate that Kalirin binds to and colocalizes with the TrkA neurotrophin receptor in neurons. In PC12 cells, inhibition of Kalirin expression using antisense RNA decreased nerve growth factor (NGF)-induced TrkA autophosphorylation and process extension. Kalirin overexpression potentiated neurotrophin-stimulated TrkA autophosphorylation and neurite outgrowth in PC12 cells at a low …

Dynamic Matrix Composition In Engineered Cartilage With Stochastic Supplementation Of Growth Factors, Asit K. Saha, J. (Jagannath) Mazumdar, Sean S. Kohles

Mechanical and Materials Engineering Faculty Publications and Presentations

Dynamic extracellular matrix (ECM) synthesis is explored in a hypothesized engineered cartilage construct. Growth (α) and decay (β) rate parameters are developed from a previous engineered cartilage model. The presented mathematical model was constructed from the parameterized experimental data using a deterministic and stochastic examination of ECM synthesis based on a negative feedback control mechanism. A growth factor supplementation is incorporated in a probabilistic mathematical approach. The growth factor component modified an initial deterministic model through a Gaussian white noise fluctuation. As the primary constituents of ECM, the mathematical tool is intended to characterize the probable steady state distribution of …

A New Interpretation Of The Drug Levodopa In The Treatment Of Parkinson's Disease, Joanne T. Vannah

Graduate Masters Theses

An argument for levodopa induced dyskinesias (LID) as an expression of long term potentiation (LTP) in the striatum is presented. Normally, with an intact nigrostriatal dopamine (DA) input, long term depression (LTD) is expressed in the striatum, however, striatal LTD is lost following DA denervation and chronic levodopa treatment. It is possible that these changes in synaptic efficacy are due to two other chemical modulators, achetylcholine (ACh) and glutamate, which in turn leads to the induction of striatal LTP. ACh and glutamate may produce these changes in motor behavior by affecting the striosomal pathway in addition to their effect on …

Endothelial Cell Pseudopods And Angiogenesis Of Breast Cancer Tumors, Ivan L. Cameron, Nicholas Short, Luzhe Sun, W. Elaine Hardman

Biochemistry and Microbiology

Background

A neoplastic tumor cannot grow beyond a millimeter or so in diameter without recruitment of endothelial cells and new blood vessels to supply nutrition and oxygen for tumor cell survival. This study was designed to investigate formation of new blood vessels within a human growing breast cancer tumor model (MDA MB231 in mammary fat pad of nude female mouse). Once the tumor grew to 35 mm³, it developed a well-vascularized capsule. Histological sections of tumors greater than 35 mm³were stained with PAS, with CD-31 antibody (an endothelial cell maker), or with hypoxia inducible factor 1α …

A Virtual Model Of The Human Cervical Spine For Physics-Based Simulation And Applications, Hyung Soo Ahn

Theses and Dissertations (ETD)

Utilizing recent advances in computer technology, Our Biomechanics Laboratory have made an effort to integrate computer animation and engineering analysis software into biomedical research, specifically towards simulation and animation of in vitro experimentation of the human cervical spine in the virtual world. The objectives of this study were to develop a virtual model of the human cervical spine for physics-based simulation and to apply the virtual model to studies of different surgical procedures and instrumentation.

A process for creating an accurate virtual model of the human cervical spine was developed. The model consisted of seven vertebrae (C2-T1) connected with soft …

Stim1, An Essential And Conserved Component Of Store-Operated Ca2+ Channel Function, Jack Roos, Paul J. Digregorio, Andriy V. Yeromin, Kari Ohlsen, Maria I. Lioudyno, Shenyuan L. Zhang, Olga Safrina, J. Ashot Kozak, Steven L. Wagner, Michael D. Cahalan, Gönül Veliçelebi, Kenneth A. Stauderman

Neuroscience, Cell Biology & Physiology Faculty Publications

Store-operated Ca²⁺ (SOC) channels regulate many cellular processes, but the underlying molecular components are not well defined. Using an RNA interference (RNAi)-based screen to identify genes that alter thapsigargin (TG)-dependent Ca²⁺ entry, we discovered a required and conserved role of Stim in SOC influx. RNAi-mediated knockdown of Stim in Drosophila S2 cells significantly reduced TG-dependent Ca²⁺ entry. Patch-clamp recording revealed nearly complete suppression of the Drosophila Ca²⁺ release-activated Ca²⁺(CRAC) current that has biophysical characteristics similar to CRAC current in human T cells. Similarly, knockdown of the human homologue STIM1 significantly reduced CRAC channel activity …

Effects Of A Small Mammalian Herbivore On A Grassland Undergoing Restoration, Margaret Murphy

Masters Theses & Specialist Projects

This thesis examines the effects of the prairie vole, Microtus ochrogaster, on a grassland undergoing restoration. The study addresses these effects with respect to treatment plots (vole-enhanced enclosures and vole-excluded exclosures) and control plots, which have not had the small mammal community manipulated. This study has also been accepted as a manuscript for publication in the "Proceedings of the 18th North American Prairie Conference."1 Two ancillary studies were also conducted. The first, reported in Appendix I, examines the composition and effects on plant community structure by the unmanipulated, small mammal community from the control plots within the area undergoing restoration …

Modeling Of Immunoglobulin Uptake By N,N,N′,N′-Ethylenediaminetetramethylenephosphonic Acid-Modified Zirconia Particles Under Static And Dynamic Conditions, Sabyasachi Sarkar, Anuradha Subramanian

Papers in Biotechnology

A matrix developed from N,N,N′,N′-ethylenediaminetetramethylenephosphonic acid-modified zirconia beads (further referred to as r_PEZ); 25–38 μm in diameter and with a pore size of 22 ± 3 nm, was utilized for the separation of immunoglobulins (Igs). r_PEZ has been shown to bind to various Igs originating from a wide variety of species. To understand the mechanisms controlling the uptake of Igs by r_PEZ, static protein uptake experiments were carried out. The protein uptake profiles were further modeled with a kinetic rate constant model. Individual studies were undertaken for human immunoglobulin A, G and M (HIgA, HIgG and HIgM). The kinetic rate …

A Developmental Switch In The Response Of Drg Neurons To Ets Transcription Factor Signaling, Simon Hippenmeyer, Eline Vrieseling, Markus Sigrist, Thomas Portmann, Celia Laengle, David R. Ladle, Silvia Arber

Neuroscience, Cell Biology & Physiology Faculty Publications

Two ETS transcription factors of the Pea3 subfamily are induced in subpopulations of dorsal root ganglion (DRG) sensory and spinal motor neurons by target-derived factors. Their expression controls late aspects of neuronal differentiation such as target invasion and branching. Here, we show that the late onset of ETS gene expression is an essential requirement for normal sensory neuron differentiation. We provide genetic evidence in the mouse that precocious ETS expression in DRG sensory neurons perturbs axonal projections, the acquisition of terminal differentiation markers, and their dependence on neurotrophic support. Together, our findings indicate that DRG sensory neurons exhibit a temporal …

Somatostatin Regulates Intracellular Signaling In Human Bronchial Smooth Muscle Cells, Michael J. Alfonzo

Seton Hall University Dissertations and Theses (ETDs)

Somatostatin (somatotropin release inhibitory factor; SRIF), is an endogenous peptide family that controls cellular secretion and proliferation. While SRIF's cognate receptors and associated actions have been clearly identified in a range of tissues, such as the endocrine, gastrointestinal and immune systems, a role in human lung physiology remains unknown. Using primary human bronchial smooth muscle cells (hBSMC) as a model for studying SRIF's actions, we have investigated whether SRIF receptors are present and functional in human bronchial smooth muscle. Reverse transcriptase- polymerase chain reaction (RT-PCR) analysis ofhBSMC total mRNA demonstrated the presence of the sst, receptor subtype, providing a molecular …

Dietary Omega-3 Fatty Acids And Ionizing Irradiation On Human Breast Cancer Xenograft Growth And Angiogenesis, W. Elaine Hardman, Luzhe Sun, Nicholas Short, Ivan L. Cameron

Biochemistry and Microbiology

Background

The effects of an omega-3 (n-3) fatty acid enriched diet alone and in combination with gamma irradiation (IR) therapy in nude mice bearing a human MDA-MB231 breast cancer xenograft were tested. The cancer cells were injected into the mammary fat pad of young female mice. Six weeks later, mice were randomly divided into two diet groups: 1) mice with 10% corn oil (rich in omega 6 fatty acids) in their food, 2) mice consuming a 10% fat diet that was enriched in n-3 fatty acids. After two weeks on the diet, treatment with 200 cGy of IR every second …

Evaluation Of Glucocorticoid Sensitivity In 697 Pre-B Acute Lymphoblastic Leukemia Cells After Overexpression Or Silencing Of Map Kinase Phosphotase-1, Marc T. Abrams, Noreen Robertson, Gerald Litwack, Eric Wickstrom

Department of Biochemistry and Molecular Biology Faculty Papers

PURPOSE: To determine the effect of reducing MAP kinase phosphatase-1 (MKP-1) levels on cell death induced by glucocorticoid (GC) or hydroxyurea (HU) treatment in the human pre-B acute lymphoblastic leukemia cell line 697.

METHODS: Stable MKP-1 overexpressing transformants of the 697 pre-B ALL cell line were created and tested for sensitivity to the GC triamcinolone acetonide (TA) and HU, and compared to a control 697 cell line containing normal MKP-1 expression levels. Small interfering RNAs (siRNAs) were designed to inhibit MKP-1 expression and evaluated for their effect on GC-mediated cell death.

RESULTS: MKP-1 overexpression caused a phenotype of partial resistance …

Ocular Surface Epithelia Contain Abcg2-Dependent Side Population Cells Exhibiting Features Associated With Stem Cells., Murat T Budak, Onder S Alpdogan, Mingyuan Zhou, Robert M Lavker, M A Murat Akinci, J Mario Wolosin

Department of Medical Oncology Faculty Papers

When cell populations are incubated with the DNA-binding dye Hoechst 33342 and subjected to flow cytometry analysis for Hoechst 33342 emissions, active efflux of the dye by the ABCG2/BCRP1 transporter causes certain cells to appear as a segregated cohort, known as a side population (SP). Stem cells from several tissues have been shown to possess the SP phenotype. As the lack of specific surface markers has hindered the isolation and subsequent biochemical characterization of epithelial stem cells this study sought to determine the existence of SP cells and expression of ABCG2 in the epithelia of the ocular surface and evaluate …

Molecular And Clinical Analyses Of Greig Cephalopolysyndactyly And Pallister-Hall Syndromes: Robust Phenotype Prediction From The Type And Position Of Gli3 Mutations, Jennifer J. Johnston, Isabelle Olivos-Glander, Christina Killoran, David Tilstra Md

Articles

Mutations in the GLI3 zinc-finger transcription factor gene cause Greig cephalopolysyndactyly syndrome (GCPS) and Pallister-Hall syndrome (PHS), which are variable but distinct clinical entities. We hypothesized that GLI3 mutations that predict a truncated functional repressor protein cause PHS and that functional haploinsufficiency of GLI3 causes GCPS. To test these hypotheses, we screened patients with PHS and GCPS for GLI3 mutations. The patient group consisted of 135 individuals: 89 patients with GCPS and 46 patients with PHS. We detected 47 pathological mutations (among 60 probands); when these were combined with previously published mutations, two genotype-phenotype correlations were evident. First, GCPS was …

26Al-Containing Acidic And Basic Sodium Aluminum Phosphate Preparation And Use In Studies Of Oral Aluminum Bioavailability From Foods Utilizing 26Al As An Aluminum Tracer, Robert A. Yokel, Aaron A. Urbas, Robert A. Lodder, John P. Selegue, Rebecca L. Florence

Pharmaceutical Sciences Faculty Publications

We synthesized ²⁶Al-containing acidic and basic (alkaline) sodium aluminum phosphates (SALPs) which are FDA-approved leavening and emulsifying agents, respectively, and used them to determine the oral bioavailability of aluminum incorporated in selected foods. We selected applicable methods from published syntheses (patents) and scaled them down (∼3000- and 850-fold) to prepare ∼300–400 mg of each SALP. The ²⁶Al was incorporated at the beginning of the syntheses to maximize ²⁶Al and ²⁷Al equilibration and incorporate the ²⁶Al in the naturally-occurring Al-containing chemical species of the products. Near infrared spectroscopy (NIR) and X-ray powder diffraction (XRD) were used …

Sara Is An Essential Positive Regulator Of Staphylococcus Epidermidis Biofilm Development, Maria A. Tormo, Miguel Marti, Jaione Valle, Adhar C. Manna

Dartmouth Scholarship

Staphylococcus epidermidis biofilm formation is associated with the production of the polysaccharide intercellular adhesin (PIA)--poly-N-acetylglucosamine polysaccharide (PNAG) by the products of the icaADBC operon. Recent evidence indicates that SarA, a central regulatory element that controls the production of Staphylococcus aureus virulence factors, is essential for the synthesis of PIA/PNAG and the ensuing biofilm development in this species. Based on the presence of a sarA homolog, we hypothesized that SarA could also be involved in the regulation of the biofilm formation process in S. epidermidis. To investigate this, we constructed nonpolar sarA deletions in two genetically unrelated S. epidermidis clinical strains, …

Identification Of A Tcpc-Tcpq Outer Membrane Complex Involved In The Biogenesis Of The Toxin-Coregulated Pilus Of Vibrio Cholerae, Niranjan Bose, Ronald K. Taylor

Dartmouth Scholarship

The toxin-coregulated pilus (TCP) of Vibrio cholerae and the soluble TcpF protein that is secreted via the TCP biogenesis apparatus are essential for intestinal colonization. The TCP biogenesis apparatus is composed of at least nine proteins but is largely uncharacterized. TcpC is an outer membrane lipoprotein required for TCP biogenesis that is a member of the secretin protein superfamily. In the present study, analysis of TcpC in a series of strains deficient in each of the TCP biogenesis proteins revealed that TcpC was absent specifically in a tcpQ mutant. TcpQ is a predicted periplasmic protein required for TCP biogenesis. Fractionation …

Automated Migration Analysis Based On Cell Texture: Method & Reliability, Jianfeng Qin, Thomas W. Chittenden, Ling Gao, Justin D D. Pearlman

Dartmouth Scholarship

Background: In this paper, we present and validate a way to measure automatically the extent of cell migration based on automated examination of a series of digital photographs. It was designed specifically to identify the impact of Second Hand Smoke (SHS) on endothelial cell migration but has broader applications. The analysis has two stages: (1) preprocessing of image texture, and (2) migration analysis.

Results: The output is a graphic overlay that indicates the front lines of cell migration superimposed on each original image, with automated reporting of the distance traversed vs. time. Expert preference compares to manual placement of leading …

Role For Akt3/Protein Kinase Bγ In Attainment Of Normal Brain Size, Rachel M. Easton, Han Cho, Kristin Roovers, Diana W. Shineman

Dartmouth Scholarship

Studies of Drosophila and mammals have revealed the importance of insulin signaling through phosphatidylinositol 3-kinase and the serine/threonine kinase Akt/protein kinase B for the regulation of cell, organ, and organismal growth. In mammals, three highly conserved proteins, Akt1, Akt2, and Akt3, comprise the Akt family, of which the first two are required for normal growth and metabolism, respectively. Here we address the function of Akt3. Like Akt1, Akt3 is not required for the maintenance of normal carbohydrate metabolism but is essential for the attainment of normal organ size. However, in contrast to Akt1^−/− mice, which display a …

Rat/Mgra, A Regulator Of Autolysis, Is A Regulator Of Virulence Genes In Staphylococcus Aureus, Susham Ingavale, Willem Van Wamel, Thanh T. Luong, Chia Y. Lee, Ambrose L. Cheung

Dartmouth Scholarship

We have previously identified mgrA (rat) as a regulator of autolysis in Staphylococcus aureus. Besides its effect on autolytic activity, we recently found alterations in the expression of regulator and target virulence genes in the mgrA mutant. Northern analysis and transcription fusion assays showed that inactivation of mgrA has led to the downregulation of RNAIII of agr and hla and upregulation of sarS and spa. Although both SarA and agr are activators of α-hemolysin and a repressors of protein A synthesis, we found that the transcription of sarA was not affected in the mgrA mutant and …

Defective B Cell Responses In The Absence Of Sh2d1a, Massimo Morra, Robert A. Barrington, Ana C. Abadia-Molina, Susumo Okamoto, Aimee Julien, Charles A. Gullo Phd, Anuj Kalsy, Matthew J. Edwards, Gang Chen, Rosanne Spolski, Warren J. Leonard, Brigitte T. Huber, Persephone Borrow, Christine A. Biron A. Biron, Abhay R. Satoskar, Michael C. Carroll, Cox Terhorst

Biochemistry and Microbiology

More than half of patients with X-linked lympho-proliferative disease, which is caused by a defect in the intracellular adapter protein SH2D1A, suffer from an extreme susceptibility to Epstein-Barr virus. One-third of these patients, however, develop dysgammaglobulenemia without an episode of severe mononucleosis. Here we show that in SH2D1A-/- mice, both primary and secondary responses of all Ig subclasses are severely impaired in response to specific antigens. Because germinal centers were absent in SH2D1A-/- mice upon primary immunization, and because SH2D1A was detectable in wt germinal center B cells, we examined whether SH2D1A-/- B cell functions were impaired. Using the adoptive …

5-Ht1b Receptor-Mediated Presynaptic Inhibition Of Gaba Release In The Suprachiasmatic Nucleus, Jayne R. Bramley, Patricia J. Sollars, Gary E. Pickard, F. Edward Dudek

School of Veterinary and Biomedical Sciences: Faculty Publications

The suprachiasmatic nucleus (SCN) receives a dense serotonergic innervation that modulates photic input to the SCN via serotonin 1B (5-HT_1B) presynaptic receptors on retinal glutamatergic terminals. However, the majority of 5-HT_1B binding sites in the SCN are located on nonretinal terminals and most axonal terminals in the SCN are GABAergic. We therefore tested the hypothesis that 5-HT_1B receptors might also be located on SCN GABAergic terminals by examining the effects of the highly selective 5-HT_1B receptor agonist CP-93,129 on SCN miniature inhibitory postsynaptic currents (mIPSCs). Whole cell patch-clamp recordings of mIPSCs were obtained from rat …

Two-Dimensional Fluorescence Difference Gel Electrophoresis Analysis Of The Urine Proteome In Human Diabetic Nephropathy, Kumar Sharma, Sohee Lee, Steven Han, Sungchun Lee, Barbara Francos, Peter Mccue, Richard Wassell, M. Alexander Shaw, Satish P. Ramachandrarao

Department of Medicine Faculty Papers

Urinary proteins may provide clues regarding pathogenesis of kidney disease as well as providing markers of disease activity. We employed two-dimensional differential in-gel electrophoretic analysis (2-D DIGE) to assess multiple urine samples in patients with diabetic nephropathy. Patient samples were collected as timed overnight collections. All the patients had longstanding diabetes, impaired renal function, and overt proteinuria. Control and patient urinary protein were analyzed by 2-D DIGE and DeCyder analysis. Ninety-nine spots were significantly regulated in the urine proteome of the diabetic samples, with 63 up- and 36 down-regulated. One spot corresponding to a pI 5–6 and a molecular weight …

A Three-Component Regulatory System Regulates Biofilm Maturation And Type Iii Secretion In Pseudomonas Aeruginosa, Sherry L. Kuchma, John P. Connolly, George A. O'Toole

Dartmouth Scholarship

Biofilms are structured communities found associated with a wide range of surfaces. Here we report the identification of a three-component regulatory system required for biofilm maturation by Pseudomonas aeruginosa strain PA14. A transposon mutation that altered biofilm formation in a 96-well dish assay originally defined this locus, which is comprised of genes for a putative sensor histidine kinase and two response regulators and has been designated sadARS. Nonpolar mutations in any of the sadARS genes result in biofilms with an altered mature structure but do not confer defects in growth or early biofilm formation, swimming, or twitching motility. After …

Multiple Metabolic Hits Converge On Cd36 As Novel Mediator Of Tubular Epithelial Apoptosis In Diabetic Nephropathy, Katalin Susztack, Emilio Ciccone, Peter Mccue, Kumar Sharma, Erwin Böttinger

Department of Medicine Faculty Papers

Diabetic nephropathy (DNP) is a common complication of type 1 and type 2 diabetes mellitus and the most common cause of kidney failure. While DNP manifests with albuminuria and diabetic glomerulopathy, its progression correlates best with tubular epithelial degeneration (TED) and interstitial fibrosis. However, mechanisms leading to TED in DNP remain poorly understood.