Abstract 07: Collecting Duct (Pro) Renin Receptor(PRR) Promotes Kidney Fibrosis Via Macrophage Alternative Activation Mediated By Soluble PRR (sPRR)-Dependent Activation Of Yap/Taz Axis

Hypertension ◽  
2021 ◽  
Vol 78 (Suppl_1) ◽  
Author(s):  
Ye Feng ◽  
Shiying Xie ◽  
Renfei Luo ◽  
Fei Wang ◽  
Tianxin Yang
Keyword(s):  
Mrna Expression ◽  
Collecting Duct ◽  
Mannose Receptor ◽  
Fine Tuning ◽  
Alternative Activation ◽  
Binding Motif ◽  
M2 Macrophage ◽  
Water Excretion ◽  
Arginase 1 ◽  
M2 Polarization

Renal collecting duct (CD), an important site for fine-tuning urinary Na + and water excretion, is not traditionally thought to play a role in pathogenesis of chronic kidney disease. In the present study, we examined a profibrotic role of CD PRR in a mouse model of unilateral ureteral obstruction (UUO) and further defined the underlying mechanism involving soluble PRR (sPRR)-dependent activation of alternative macrophages activation. We subjected mice with CD-specific deletion of PRR (CD PRR KO) and their floxed controls to UUO or sham surgery. After 7 days of UUO, CD PRR KO decreased the fibronectin (28.6±6.8%) and α-SMA (39.2±7.8%) protein expression in obstructed kidneys. The Masson’s trichrome staining data also showed that CD PRR KO significantly attenuated UUO-induced collagen deposition and histological damage in the kidney. In parallel, CD PRR KO reduced TGF-β1 (56.7±3.2%) and TGF-β2 (53±1.2%) mRNA expression in obstructed kidneys. Moreover, in macrophages sorted from obstructed kidneys of CD PRR KO mice showed a significantly reduced of M2 macrophage markers such as mannose receptor ( MR ) (58.7±2.1%), arginase-1 ( Arg-1 ) (50±1.5%), chitinase-like lectins ( YM-1 ) (59.3±1.9%), inflammatory zone-1 ( Fizz1 ) (39.1±4.1%) mRNA expression and Yes-associated protein ( Yap ) (77±6.8%)/ transcriptional coactivator with PDZ-binding motif ( Taz ) (54.5±1.8%) mRNA expression compared with macrophages sorted from obstructed kidneys of floxed mice. Meanwhile, plasma sPRR was elevated in floxed mice by UUO and this elevation was blunted by CD PRR KO (23.7±0.4%). Administration of site-1 protease (S1P) inhibitor PF-429242 to C57BL/6 mice with UUO almost completely recapitulated the antifibrotic action as well as the inhibitory effect on M2 activation of CD PRR KO. In bone marrow-derived macrophages, sPRR-His treatment promoted macrophage M2 polarization, fibrosis and Yap/Taz expression. Overall, these results suggest that activation of CD PRR releases sPRR that activates M2 polarization via Yap/Taz axis, leading to renal fibrosis during UUO.

Tet2 Is a Novel Regulator of Murine Macrophage Differentiation and Polarization

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 646-646
Author(s):  
Alyssa Cull ◽  
Brooke Snetsinger ◽  
Michael J. Rauh
Keyword(s):  
Gene Expression ◽  
Blood Plasma ◽  
Mrna Expression ◽  
Conflicts Of Interest ◽  
Environmental Influence ◽  
Macrophage Polarization ◽  
M2 Macrophage ◽  
Mrna Levels ◽  
Hematopoietic Stem ◽  
Arginase 1

Abstract Introduction: The epigenetic regulator, TET2, catalyzes the conversion of methylcytosine to 5-hydroxymethylcytosine. Inactivating TET2 mutations are common in myeloid cancers such as chronic myelomonocytic leukemia (CMML). Although TET2 has been characterized in hematopoietic stem and progenitor cells, little is known about its role in disease-relevant monocytes/macrophages (MΦ). Previously, we found increased expression of M2 MΦ-associated arginase 1 (Arg1) in TET2 -mutant CMML and Tet2 -deficient MΦ. Therefore, our goals were to (1) characterize Tet family expression during normal murine MΦ differentiation and polarization, (2) determine the effect of Tet2 -deficiency on broader M1-M2 MΦ spectrum gene signatures. Methods: Hematopoietic-specific Tet2+/- and Tet2-/- knockout mice were generated by breeding floxed Tet2(f/f) with Vav-Cre mice (JAX), in accordance with Queen's University's Animal Care protocols. MΦs obtained by peritoneal lavage (PMΦ) and bone marrow differentiation (BMMΦ) from 9-13 week old Tet2-/- and 20-40 week old Tet2+/- mice were treated with an M1 stimulus (100ng/mL LPS) or an M2 stimulus (10ng/mL Il-4). Comparative gene expression analysis was conducted using a 591 candidate gene Mouse Immunology Gene Expression CodeSet (NanoString). Blood plasma samples collected from Tet2f/f and Tet2-/- mice were sent for cytokine/chemokine array analysis (Eve Technologies). Results: A survey of Tet mRNA expression in wild-type C57BL/6 mouse whole BM showed that Tet1 was most abundantly expressed, with Tet2 and Tet3 having relative abundances of 0.56±0.05 and 0.09±0.01 respectively. In contrast, Tet2 expression peaked, while Tet1 expression diminished during BMMΦ differentiation. Suggesting a functional role, loss of murine Tet2 is associated with skewed myelomonocytic differentiation (i.e. CMML phenotype). In terminally-differentiated MΦ, Tet2 was the most abundantly expressed Tet gene, suggesting MΦ-specific functions. Consistent with this, following a 3-hour LPS stimulation, Tet2 mRNA levels increased 2- to 4-fold, whereas Il-4 failed to induce a similar increase in expression. Overall, our results suggested that Tet2 plays a role in M1 but not M2 macrophage polarization. Based on these findings, we hypothesized that loss of Tet2 would lead to M1 program dysregulation. PMΦs were obtained from Tet2f/f and Tet2-/- mice (n=2/ genotype) and RNA was harvested from untreated and LPS- or Il-4-treated cells. Pools of these RNA samples were then screened using Nanostring. Overall, M1-associated markers such as Stat1, Socs1, Nfkbiz, Il-6, Il-27, Il-12, Il-1 and Ccl2 were markedly increased by 2- to 50-fold in resting Tet2-/- PMΦs compared to matched Tet2f/f samples. These same M1 genes demonstrated a reduced ability to be induced by LPS treatment. We also found that while the expression of most M2 genes was similar in controls versus knockouts, Il-1rn and Arg1 were overexpressed, and Marco was decreased. This suggested that Tet2 -deficient MΦs possess a complex phenotype with a potential homeostatic response to M1 gene dysregulation. We have previously seen variable upregulation of Arg1 in mouse BMMΦs and PMΦs. Approximately 60% of Tet2-deficient mice (+/- and -/-) (n=20) tested for MΦ Arg1 mRNA expression demonstrated 2- to 90-fold increases in Arg1 compared to pooled Tet2f/f controls (n=5). We were interested in investigating the underlying mechanisms contributing to this dramatic increase in expression. Using Nanostring on pooled Tet2-deficient PMΦs with low (n=7) or high (n=8) Arg1 mRNA expression, we were able to identify genes whose expression significantly correlated with Arg1 overexpression: Cxcl3 (p=0.0329), Ppbp (p=0.0015), Cxcl1 (p=0.0104) and Ccl6 (p=0.0185). Of note, Ppbp was the most divergently expressed gene (46-fold difference) in Arg1 low vs Arg1 high macrophages, followed by Arg1 itself (14-fold difference). Suggesting a further environmental influence, blood plasma levels of TNF-alpha, Il-1b, Il-4, Il-10, Il-12 and Il-13 were significantly elevated in mice with high PMΦ Arg1 mRNA expression (n=5) compared to those with low expression (n=10). Conclusions: Tet2 is a novel regulator of murine MΦ, induced during MΦ differentiation and M1-polarization. Tet2 loss leads to complex disruption of the M1-M2 spectrum. We are currently exploring whether human TET2 mutations contribute to the abnormal immune environment of myeloid cancers. Disclosures No relevant conflicts of interest to declare.

scholarly journals Screening Five Qi-Tonifying Herbs on M2 Phenotype Macrophages

2019 ◽  
Vol 2019 ◽  
pp. 1-8 ◽  
Author(s):  
Yi-Xin Jiang ◽  
Yan Chen ◽  
Yue Yang ◽  
Xiao-Xia Chen ◽  
Dan-Dan Zhang
Keyword(s):  
Molecular Mechanisms ◽  
Immune Therapy ◽  
Ethanol Extract ◽  
Mannose Receptor ◽  
Inhibitory Effect ◽  
M2 Macrophages ◽  
Arginase 1 ◽  
M2 Polarization ◽  
New Strategy ◽  
M2 Phenotype

Tumor-associated macrophages (TAMs) with M2 phenotype play an essential role in tumor microenvironment (TME) during the progression and development of numerous cancers and associated with poor prognosis. Thus, regulation of TAMs polarization emerged as a new strategy for tumor immune therapy. According to Traditional Chinese Medicine (TCM) theory, herbs with Qi-tonifying character are involved in improving the defense capacity of immune system. In this study, we screened extracts and ingredients from five Qi-tonifying herbs exhibiting an inhibitory effect on M2 polarization of murine macrophages RAW264.7 induced by IL-4 and IL-13. Among these candidates, total flavonoids from Glycyrrhiza Radix et Rhizoma (TFRG) and ethanol extract of Ginseng Radix et Rhizoma significantly inhibited the expression of Arginase-1 (Arg-1) (above 90% at 100μg/mL), one of the phenotype markers of M2 macrophages. The inhibition of total saponins of Ginseng Radix et Rhizoma, ethanol extract of Cordyceps, ethanol extract of Acanthopanacis senticosi Radix et Rhizoma Seu caulis, and ethanol extract of Astragali Radix reached above 50% at 100μg/mL. The inhibition of ingredients including glabridin, isoliquiritin apioside, lysionotin, cordycepin, astragaloside IV, and calycosin reached above 50% at 50μM. Then, we investigated the molecular mechanisms of TFRG. TFRG abolished the migration of murine breast cancer 4T1 stimulated by the conditioned medium from M2 macrophages (M2-CM). In addition to Arg-1, TFRG also antagonized the IL-4/13-mediated mRNA upregulation of the M2 markers including found in inflammatory zone 1 (FIZZ1), chitinase-3-like protein 3 (YM1), and mannose receptor (CD206) and upregulated the expression of inducible nitric oxide synthase (iNOS), one of the M1 markers. The further exploration showed that TFRG decreased the phosphorylation of STAT6 and increased the expression of miR-155. Our study provides a series of potential immune regulating natural products from five Qi-tonifying herbs on M2 phenotype. For instance, TFRG suppressed M2 polarization of macrophages partly by inactivating STAT6 pathway and enhanced the level of miR-155 to regulate the expressions of M1 and M2 markers.

scholarly journals Oxidized LDL Induces Alternative Macrophage Phenotype through Activation of CD36 and PAFR

2013 ◽  
Vol 2013 ◽  
pp. 1-8 ◽  
Author(s):  
Francisco J. Rios ◽  
Marianna M. Koga ◽  
Mateus Pecenin ◽  
Matheus Ferracini ◽  
Magnus Gidlund ◽  
...  
Keyword(s):  
Mrna Expression ◽  
Macrophage Activation ◽  
Oxidized Ldl ◽  
Platelet Activating Factor ◽  
Mannose Receptor ◽  
Mrna Levels ◽  
Macrophage Phenotype ◽  
Macrophage Differentiation ◽  
Arginase 1 ◽  
Pre Treatment

OxLDL is recognized by macrophage scavenger receptors, including CD36; we have recently found that Platelet-Activating Factor Receptor (PAFR) is also involved. Since PAFR in macrophages is associated with suppressor function, we examined the effect of oxLDL on macrophage phenotype. It was found that the presence of oxLDL during macrophage differentiation induced high mRNA levels to IL-10, mannose receptor, PPARγand arginase-1 and low levels of IL-12 and iNOS. When human THP-1 macrophages were pre-treated with oxLDL then stimulated with LPS, the production of IL-10 and TGF-βsignificantly increased, whereas that of IL-6 and IL-8 decreased. In murine TG-elicited macrophages, this protocol significantly reduced NO, iNOS and COX2 expression. Thus, oxLDL induced macrophage differentiation and activation towards the alternatively activated M2-phenotype. In murine macrophages, oxLDL induced TGF-β, arginase-1 and IL-10 mRNA expression, which were significantly reduced by pre-treatment with PAFR antagonists (WEB and CV) or with antibodies to CD36. The mRNA expression of IL-12, RANTES and CXCL2 were not affected. We showed that this profile of macrophage activation is dependent on the engagement of both CD36 and PAFR. We conclude that oxLDL induces alternative macrophage activation by mechanisms involving CD36 and PAFR.

scholarly journals Protective Effects of Two Safflower Derived Compounds, Kaempferol and Hydroxysafflor Yellow A, on Hyperglycaemic Stress-Induced Podocyte Apoptosis via Modulating of Macrophage M1/M2 Polarization

2020 ◽  
Vol 2020 ◽  
pp. 1-11
Author(s):  
Yuanping Li ◽  
Dan Zheng ◽  
Dayue Shen ◽  
Xilan Zhang ◽  
Xiaoyun Zhao ◽  
...  
Keyword(s):  
Survival Rate ◽  
Macrophage Polarization ◽  
Mannose Receptor ◽  
M2 Macrophage ◽  
Protective Effects ◽  
Hydroxysafflor Yellow A ◽  
Real Time Quantitative Pcr ◽  
M2 Polarization ◽  
Oxide Synthase

Objective. The primary initiating mechanism in diabetes nephropathy (DN) is hyperglycemia-induced inflammation in which macrophage and podocyte play important roles. The present research is aimed at exploring the effects of kaempferol (Ka) and hydroxysafflor yellow A (HSYA) on classically activated (M1)/alternatively activated (M2) macrophage polarization and podocyte apoptosis under hyperglycaemic conditions in vitro. Methods. (1) RAW264.7 cells were treated with 11.1 mM glucose (NG), 33.3 mM glucose (HG), Ka 4–8 μM, and HSYA 100–200 μM separately. The expressions of inducible nitric oxide synthase (iNOS), tumor necrosis factor- (TNF-) α, mannose receptor (CD206), and arginase- (Arg-) 1 were quantified by Western blotting and real-time quantitative PCR. The collected supernatants from macrophage were named as (NG) MS, (HG) MS, (Ka) MS, and (HSYA) MS. (2) The podocyte survival rate was assessed by Bromodeoxyuridine assay, while TNF-α and interleukin- (IL-) 1β levels were evaluated by Elisa. Results. (1) Compared to the HG group, the Ka and HSYA 100 μM groups decreased iNOS and TNF-α levels and increased Arg-1 and CD206 expressions significantly (protein and mRNA: p<0.05, respectively). (2) The podocyte survival rate of Ka 8 μM was higher than that of HG, and the rates of (Ka) MS and (HSYA 100 μM) MS were higher than that of (HG) MS significantly (all: p<0.05). (3) TNF-α and IL-1β levels of Ka and HSYA 100 μM were significantly lower than those of the HG group, and both levels in the (Ka) MS and (HSYA) MS were lower than those in the (HG) MS group significantly (p<0.05, respectively). Conclusion. The protective effects of Ka and HSYA on podocyte apoptosis under hyperglycemic stress are related to their modulation on M1/M2 polarization and the lowering effects on TNF-α and IL-1β levels.

scholarly journals Physiological regulation of the epithelial Na+ channel by casein kinase II

2018 ◽  
Vol 314 (3) ◽  
pp. F367-F372 ◽  
Author(s):  
Jonathan M. Berman ◽  
Elena Mironova ◽  
James D. Stockand
Keyword(s):  
Sodium Excretion ◽  
Ex Vivo ◽  
Collecting Duct ◽  
Phosphorylation Site ◽  
Animal Experiments ◽  
Physiological Role ◽  
Casein Kinase ◽  
Fine Tuning ◽  
Na Channel ◽  
Water Excretion

epithelial Na+ channel, ENaC, is the final arbiter of sodium excretion in the kidneys. As such, discretionary control of ENaC by hormones is critical to the fine-tuning of electrolyte and water excretion and, consequently, blood pressure. Casein kinase 2 (CK2) phosphorylates ENaC. Phosphorylation by CK2 is necessary for normal ENaC activity. We tested the physiological importance of CK2 regulation of ENaC as the degree to which ENaC activity is dependent on CK2 phosphorylation in the living organism is unknown. This was addressed using patch-clamp analysis of ENaC in completely split-open collecting ducts and whole animal physiological studies of sodium excretion in mice. We also used ENaC-harboring CK2 phosphorylation site mutations to elaborate the mechanism. We found that ENaC activity in ex vivo preparations of murine collecting duct had a significant decrease in activity in response to selective antagonism of CK2. In whole animal experiments selective antagonism of CK2 caused a natriuresis similar to benzamil, but not additive to benzamil, suggesting an ENaC-dependent mechanism. Regulation of ENaC by CK2 was abolished by mutation of the canonical CK2 phosphorylation sites in beta and gamma ENaC. Together, these results demonstrate that the appropriate regulation of ENaC by CK2 is necessary for the normal physiological role played by this key renal ion channel in the fine-tuning of sodium excretion.

scholarly journals Decitabine Promotes Modulation in Phenotype and Function of Monocytes and Macrophages That Drive Immune Response Regulation

Cells ◽  
2021 ◽  
Vol 10 (4) ◽  
pp. 868
Author(s):  
Fabiana Albani Zambuzi ◽  
Priscilla Mariane Cardoso-Silva ◽  
Ricardo Cardoso Castro ◽  
Caroline Fontanari ◽  
Flavio da Silva Emery ◽  
...  
Keyword(s):  
Immune Response ◽  
Hematological Malignancies ◽  
M2 Macrophage ◽  
M2 Polarization ◽  
Tnf Α ◽  
Monocytes And Macrophages ◽  
Ifn Γ ◽  
And Function ◽  
The Impact

Decitabine is an approved hypomethylating agent used for treating hematological malignancies. Although decitabine targets altered cells, epidrugs can trigger immunomodulatory effects, reinforcing the hypothesis of immunoregulation in treated patients. We therefore aimed to evaluate the impact of decitabine treatment on the phenotype and functions of monocytes and macrophages, which are pivotal cells of the innate immunity system. In vitro decitabine administration increased bacterial phagocytosis and IL-8 release, but impaired microbicidal activity of monocytes. In addition, during monocyte-to-macrophage differentiation, treatment promoted the M2-like profile, with increased expression of CD206 and ALOX15. Macrophages also demonstrated reduced infection control when exposed to Mycobacterium tuberculosis in vitro. However, cytokine production remained unchanged, indicating an atypical M2 macrophage. Furthermore, when macrophages were cocultured with lymphocytes, decitabine induced a reduction in the release of inflammatory cytokines such as IL-1β, TNF-α, and IFN-γ, maintaining IL-10 production, suggesting that decitabine could potentialize M2 polarization and might be considered as a therapeutic against the exacerbated immune response.

scholarly journals Arginase in Parasitic Infections: Macrophage Activation, Immunosuppression, and Intracellular Signals

2010 ◽  
Vol 2010 ◽  
pp. 1-10 ◽  
Author(s):  
Cinthia C. Stempin ◽  
Laura R. Dulgerian ◽  
Vanina V. Garrido ◽  
Fabio M. Cerban
Keyword(s):  
Macrophage Activation ◽  
Transforming Growth Factor ◽  
Parasite Clearance ◽  
Alternative Activation ◽  
Parasitic Infections ◽  
Activated Macrophages ◽  
Proinflammatory Response ◽  
Alternatively Activated Macrophages ◽  
Arginase 1

A type 1 cytokine-dependent proinflammatory response inducing classically activated macrophages (CaMϕs) is crucial for parasite control during protozoan infections but can also contribute to the development of immunopathological disease symptoms. Type 2 cytokines such as IL-4 and IL-13 antagonize CaMϕs inducing alternatively activated macrophages (AaMϕs) that upregulate arginase-1 expression. During several infections, induction of arginase-1-macrophages was showed to have a detrimental role by limiting CaMϕ-dependent parasite clearance and promoting parasite proliferation. Additionally, the role of arginase-1 in T cell suppression has been explored recently. Arginase-1 can also be induced by IL-10 and transforming growth factor-β(TGF-β) or even directly by parasites or parasite components. Therefore, generation of alternative activation states of macrophages could limit collateral tissue damage because of excessive type 1 inflammation. However, they affect disease outcome by promoting parasite survival and proliferation. Thus, modulation of macrophage activation may be instrumental in allowing parasite persistence and long-term host survival.

Downregulation of renal vasopressin V2 receptor and aquaporin-2 expression parallels age-associated defects in urine concentration

2004 ◽  
Vol 287 (4) ◽  
pp. F797-F805 ◽  
Author(s):  
Ying Tian ◽  
Ryota Serino ◽  
Joseph G. Verbalis
Keyword(s):  
Collecting Duct ◽  
Water Channel ◽  
Age Groups ◽  
Urine Osmolality ◽  
Brown Norway ◽  
Water Restriction ◽  
Water Excretion ◽  
F1 Hybrid ◽  
Young Rats ◽  
Aquaporin 2

Renal concentrating ability is known to be impaired with aging. The antidiuretic hormone AVP plays an important role in renal water excretion by regulating the membrane insertion and abundance of the water channel aquaporin-2 (AQP2); this effect is primarily mediated via the V2 subtype of the AVP receptor (V2R). This study evaluated the hypothesis that decreased renal sensitivity to AVP, with subsequent altered renal AQP2 expression, contributes to the reduced urinary concentrating ability with aging. Our results show that under baseline conditions, urine osmolality is significantly lower in aged Fischer 344 and Brown-Norway F1 hybrid (F344BN) rats despite equivalent plasma AVP concentrations as in young rats. Levels of kidney V2R mRNA expression and AQP2 abundances were also significantly decreased in aged F344BN rats, as was AQP2 immunostaining in collecting duct cells. In response to moderate water restriction, urine osmolality increased by significantly lesser amounts in aged F344BN rats compared with young rats despite similar increases in plasma AVP levels. Moderate water restriction induced equivalent relative increases in renal AQP2 abundances in all age groups but resulted in significantly lower abundances in total kidney AQP2 protein in aged compared with young F344BN rats. These results therefore demonstrate a functional impairment of renal concentrating ability in aged F344BN rats that is not due to impaired secretion of AVP but rather appears to be related to impaired responsiveness of the kidney to AVP that is secondary, at least in part, to a downregulation of renal V2R expression and AQP2 abundance.

Renal NG2-expressing cells have macrophage-like phenotype and facilitate renal recovery after ischemic injury

2021 ◽  
Author(s):  
Wararat Kittikulsuth ◽  
Daisuke Nakano ◽  
Kento Kitada ◽  
Norio Suzuki ◽  
Masayuki Yamamoto ◽  
...  
Keyword(s):  
Ischemia Reperfusion ◽  
Ischemic Injury ◽  
Recovery Process ◽  
Mannose Receptor ◽  
M2 Macrophage ◽  
Debris Accumulation ◽  
Cellular Debris ◽  
Brain Pericytes ◽  
Anti Inflammatory Cytokine

Pericytes play an important role in the recovery process after ischemic injury of many tissues. Brain pericytes in the peri-infarct area express macrophage markers in response to injury stimuli and are involved in neovascularization. In the kidney, nerve/glial antigen 2 (NG2)+ pericytes have been found to accumulate after renal injury. These accumulated NG2+ cells are not involved in scar formation. However, the role of accumulated NG2+ cells in injured kidneys remains unknown. Here, using a reversible ischemic reperfusion model, we found that renal NG2+ cells were increased in injured kidneys and expressed macrophage markers (CD11b or F4/80) on day 3 after reperfusion. Isolated NG2+ cells from ischemia/reperfusion (I/R) kidneys also had phagocytic activity and expressed anti-inflammatory cytokine genes, including mannose receptor and IL-10. These macrophage-like NG2+ cells did not likely differentiate into myofibroblasts because they did not increase α-SMA expression. Intravenous transfusion of renal NG2+ cells isolated from donor mice on day 3 after reperfusion into recipient mice on day 1 after I/R surgery revealed that NG2+ cell-injected mice had lower plasma blood urea nitrogen, reduced KIM-1 mRNA expression, ameliorated renal damage, and reduced cellular debris accumulation than PBS-injected mice on day 5 after reperfusion. In conclusion, these data suggest that renal NG2+ cells have an M2 macrophage-like ability and play a novel role in facilitating the recovery process after renal I/R injury.

Lack of vasopressin-independent upregulation of AQP-2 gene expression in homozygous Brattleboro rats

1999 ◽  
Vol 277 (2) ◽  
pp. R427-R433 ◽  
Author(s):  
Takako Saito ◽  
San-E Ishikawa ◽  
Sei Sasaki ◽  
Minori Higashiyama ◽  
Shoichiro Nagasaka ◽  
...  
Keyword(s):  
Gene Expression ◽  
Mrna Expression ◽  
Water Deprivation ◽  
Collecting Duct ◽  
Renal Medulla ◽  
Brattleboro Rats ◽  
Severe Dehydration ◽  
Urinary Osmolality ◽  
Independent Mechanism ◽  
Collecting Duct Cells

Arginine vasopressin (AVP) plays an important role in the expression of aquaporin (AQP-2) in the collecting duct. The present study was undertaken to determine whether there is an AVP-independent regulation of AQP-2 gene expression in homozygous Brattleboro rats in which endogenous AVP is absent. Exogenous administration of 1-deamino-8-d-AVP produced an antidiuresis and expressed AQP-2 mRNA and AQP-2 protein in the renal medulla of the homozygous Brattleboro rats. Twelve hours of water deprivation produced severe dehydration in the homozygous Brattleboro rats, such that urinary osmolality increased from 200 to 649 mosmol/kgH2O. However, no increase in AQP-2 mRNA expression was observed after this dehydration, and the medullary tissue content and urinary excretion of AQP-2 also remained unchanged. Increases in AQP-2 mRNA expression and AQP-2 protein were evident in Long-Evans rats after 64 h of water deprivation, with a severity of dehydration almost equal to the 12-h dehydrated, homozygous Brattleboro rats. These results indicate the lack of an AVP-independent mechanism for upregulating AQP-2 mRNA expression in renal collecting duct cells.

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