A5100348438- Hormonal Regulation and Hypertension
- Inflammatory mediators and NSAID effects
- Renin-Angiotensin System Studies
- Chronic Kidney Disease and Diabetes
- Renal Diseases and Glomerulopathies
- Acute Kidney Injury Research
- Eicosanoids and Hypertension Pharmacology
- Ion Transport and Channel Regulation
- Estrogen and related hormone effects
- Receptor Mechanisms and Signaling
- Pharmacogenetics and Drug Metabolism
- Dialysis and Renal Disease Management
- TGF-β signaling in diseases
- Autophagy in Disease and Therapy
- Pancreatic function and diabetes
- Cell Adhesion Molecules Research
- Metabolism, Diabetes, and Cancer
- Sodium Intake and Health
- Adipose Tissue and Metabolism
- Nitric Oxide and Endothelin Effects
- Immune cells in cancer
- Electrolyte and hormonal disorders
- Organ Donation and Transplantation
- S100 Proteins and Annexins
- Blood Pressure and Hypertension Studies
Vanderbilt University
2015-2024
Vanderbilt University Medical Center
2009-2024
Hypertension Institute
2006-2022
Nanjing Medical University
2022
Temple University
2016
Northwest A&F University
2016
Peking University
2016
Xuzhou Medical College
2014-2015
Children's Hospital of Fudan University
2014
Tongji University
2013
Functionally significant polymorphisms in endothelial nitric oxide synthase (eNOS) and reduced vascular eNOS activity have been associated with increased human diabetic nephropathy (DN), but the pathogenic role of deficiency development DN has not yet confirmed. This study characterizes severity eNOS(-/-) mice that were backcrossed to C57BLKS/J db/db mice. Although hyperglycemia was similar mice, by 26 wk, exhibited dramatic albuminuria, arteriolar hyalinosis, glomerular basement membrane...
Sirtuin 1 (Sirt1) is a NAD+-dependent deacetylase that exerts many of the pleiotropic effects oxidative metabolism. Due to local hypoxia and hypertonicity, renal medulla subject extreme stress. Here, we set out investigate role Sirt1 in kidney. Our initial analysis indicated it was abundantly expressed mouse medullary interstitial cells vivo. Knocking down expression primary substantially reduced cellular resistance stress, while pharmacologic activation using either resveratrol or SRT2183...
The epidermal growth factor receptor (EGFR) is the prototypical member of a family membrane-associated intrinsic tyrosine kinase receptors, ErbB family. EGFR activated by multiple ligands, including EGF, transforming (TGF)-α, HB-EGF, betacellulin, amphiregulin, epiregulin, and epigen. expressed in organs plays important roles proliferation, survival, differentiation both development normal physiology, as well pathophysiological conditions. In addition, transactivation underlies some biologic...
We have previously shown that in rat renal cortex, cyclooxygenase-2 (COX-2) expression is localized to cTALH cells the region of macula densa, and dietary salt restriction increases COX-2 expression. Administration angiotensin converting inhibitor, captopril, further increased mRNA cortical immunoreactivity, with most pronounced densa. an AT1 receptor antagonist, losartan, also significantly immunoreactivity. Mutant mice homozygous for both Agtr1a Agtr1b null mutations (Agtr1a-/-,Agtr1b-/-)...
Previous studies by us and others have reported renal epidermal growth factor receptors (EGFRs) are activated in models of diabetic nephropathy. In the present study, we examined effect treatment with erlotinib, an inhibitor EGFR tyrosine kinase activity, on progression nephropathy a type 1 mouse model. Inhibition activation erlotinib was confirmed decreased phosphorylation extracellular signal-related 1/2. Increased albumin/creatinine ratio mice markedly attenuated treatment....
Numerous clinical conditions can lead to organ fibrosis and functional failure. There is a great need for therapies that could effectively target pathophysiological pathways involved in fibrosis. GPR40 GPR84 are G protein-coupled receptors with free fatty acid ligands associated metabolic inflammatory disorders. Although diverse physiological processes, no evidence has demonstrated the relevance of pathways. Using PBI-4050 (3-pentylbenzeneacetic sodium salt), synthetic analog medium-chain...
In addition to its role as an essential neurotransmitter, dopamine serves important physiologic functions in organs such the kidney. Although kidney synthesizes through actions of aromatic amino acid decarboxylase (AADC) proximal tubule, previous studies have not discriminated between roles extrarenal and intrarenal overall regulation renal function. To address this issue, we generated mice with selective deletion AADC tubules (referred herein ptAadc-/- mice), which led decreases urinary...
Transcriptional intermediary factor 1 gamma (TIF1γ) may play either a potential tumor-suppressor or -promoter role in cancer. Here we report on critical of TIF1γ the progression hepatocellular carcinoma (HCC). Reduced expression was detected HCC, especially advanced HCC tissues, compared to adjacent noncancerous tissues. patients with low had shorter overall survival times and higher recurrence rates than those high expression. an independent significant risk for after curative resection. In...
TGF-β signals through a receptor complex composed of 2 type I and II (TGF-βRII) subunits. We investigated the role macrophage signaling in fibrosis after AKI mice with selective monocyte/macrophage TGF-βRII deletion (macrophage TGF-βRII-/- mice). Four weeks injury, renal TGF-β1 expression were higher WT than mice, which had decreased macrophages. The vitro chemotactic response to f-Met-Leu-Phe was comparable between bone marrow-derived monocytes (BMMs) from but BMMs did not respond TGF-β....
Significance Statement Macrophage proliferation and polarization to the M2 phenotype play a key role in AKI recovery. However, macrophages also can produce profibrotic factors their persistence may contribute interstitial fibrosis. The authors demonstrated that mice with macrophage-specific deletion of gene encoding IFN regulatory factor 4 (Irf4), mediator myeloid polarization, exhibited decreased renal fibrosis after severe AKI, association less-activated macrophages. Bone marrow–derived...
Obesity-associated complications are causing increasing morbidity and mortality worldwide. Expansion of adipose tissue in obesity leads to a state low-grade chronic inflammation dysregulated metabolism, resulting insulin resistance metabolic syndrome. Adipose macrophages (ATMs) accumulate source proinflammatory cytokines that further aggravate adipocyte dysfunction. Macrophages rich sources cyclooxygenase (COX), the rate limiting enzyme for prostaglandin E2 (PGE2) production. When mice were...
Abstract Obesity and obesity-related health complications are increasing in prevalence. Adipose tissue from obese subjects has low-grade, chronic inflammation, leading to insulin resistance. macrophages (ATMs) a source of proinflammatory cytokines that further aggravate adipocyte dysfunction. In response high fat diet (HFD), ATM numbers initially increase by proliferation resident macrophages, but subsequent increases also result infiltration chemotactic signals inflamed adipose tissue. To...
The inducible second isoform of cyclooxygenase (COX-2) that mediates inflammation also is expressed at low levels in normal adult rat kidneys and upregulated response to noninflammatory stimuli (R. C. Harris, J. A. McKanna, Y. Akai, H. R. Jacobson, N. DuBois, M. D. Breyer. Clin. Invest. 94: 2504–2510, 1994). Roles morphogenesis are indicated by reported teratogenicity COX inhibitors renal dysgenesis COX-2 knockout mice (J. E. Dinchuk, B. Car, Focht, Johnston, Jaffee, Covington, Contel, V....
The use of LiCl in clinical psychiatry is routinely complicated by overt nephrogenic diabetes insipidus (NDI), the mechanism which incompletely understood. In vitro studies indicate that lithium can induce renal medullary interstitial cell cyclooxygenase 2 (COX2) protein expression via inhibition glycogen synthase kinase-3beta (GSK-3beta). Both COX1 and COX2 are expressed kidney. Renal prostaglandins have been suggested to play an important role lithium-induced polyuria. present examined...
Colorectal cancer (CRC) is a leading cause of death, yet primary prevention remains the best approach to reducing overall morbidity and mortality. Studies have shown that COX-2-derived PGE2 promotes CRC progression, both nonselective COX inhibitors (NSAIDs) selective COX-2 (such as glucocorticoids) reduce number size colonic adenomas. However, increased gastrointestinal side effects NSAIDs cardiovascular risks limit their use in chemoprevention CRC. We found expression 11beta-hydroxysteroid...
Diabetic nephropathy (DN) is characterized by increased macrophage infiltration, and proinflammatory M1 macrophages contribute to development of DN. Previous studies us others have reported that cyclooxygenase-2 (COX-2) plays a role in polarization maintenance tissue-reparative M2 phenotype. We examined the effects COX-2 on DN type 1 diabetes. Cultured with deletion exhibited an phenotype, as demonstrated higher inducible nitric oxide synthase nuclear factor-κB levels but lower interleukin-4...
Inhibition of prostaglandin (PG) production with either nonselective or selective inhibitors cyclooxygenase-2 (COX-2) activity can induce exacerbate salt-sensitive hypertension. This effect has been previously attributed to inhibition intrinsic renal COX-2 and subsequent increase in sodium retention by the kidney. Here, we found that macrophages isolated from kidneys high-salt–treated WT mice have increased levels microsomal PGE synthase–1 (mPGES-1). Furthermore, BM transplantation (BMT)...
Previous studies by us and others have indicated that renal epidermal growth factor receptors (EGFR) are activated in models of diabetic nephropathy (DN) inhibition EGFR activity protects against progressive DN type 1 diabetes. In this study we examined whether activation would affect the development a mouse model accelerated 2 diabetes (BKS db/db with endothelial nitric oxide knockout [eNOS−/−db/db]). eNOS−/−db/db mice received vehicle or erlotinib, an inhibitor tyrosine kinase activity,...
Renal epidermal growth factor receptor (EGFR) signaling is activated in models of diabetic nephropathy (DN), and inhibition the EGFR pathway protects against development DN. We have now determined that cultured podocytes, high glucose led to increases activation but decreases autophagy activity as indicated by decreased beclin-1 LC3B autophagosome formation well increased rubicon (an inhibitor) SQSTM1 (autophagy substrate). Either genetic (small interfering [si]EGFR) or pharmacologic...
We have previously shown that in renal cortex, COX-2 expression is localized to macula densa and surrounding cortical thick ascending limb of Henle (cTALH). Dietary salt restriction increases local COX-2, which mediates renin production secretion. Given decreased luminal chloride [Cl–] at the level secretion, we investigated role extracellular ion concentration on expression. Quiescent rabbit cTALH cells were incubated a physiological solution containing high or low levels NaCl....
Production of prostaglandins involved in renal salt and water homeostasis is modulated by regulated expression the inducible form cyclooxygenase-2 (COX-2) at restricted sites rat cortex. Because inflammatory COX-2 suppressed glucocorticoids, prostaglandin levels kidney are sensitive to steroids, sensitivity COX adrenalectomy (ADX) was investigated. By 2 weeks after ADX mature rats, cortical immunoreactivity increased 10-fold thick ascending limb macula densa. The constitutive isoform, COX-1,...
Previous studies have suggested a possible role for prostaglandins (PGs) in mediating alterations nephron structure and function ensuing after renal ablation. Two isoforms of cyclooxygenase (COX) been described: constitutive (COX-1) inducible (COX-2). We examined expression these following subtotal ablation (5/6 ablation, RA) rats. In cortex, COX-2 mRNA immunoreactive protein (IP) increased progressively compared with sham-operated littermates. contrast, there were no significant changes...