scholarly journals Salt sensitive hypertension associated with stem cell defect in the renal medulla of Dahl S rats

2010 ◽  
Vol 24 (S1) ◽  
Author(s):  
Zhengchao Wang ◽  
Min Xia ◽  
Qing Zhu ◽  
Pin‐Lan Li ◽  
Ningjun Li
Keyword(s):  
Stem Cell ◽  
Renal Medulla ◽  
Salt Sensitive Hypertension ◽  
Cell Defect

Abstract 35: Transplantation of Mesenchymal Stem Cells into the Renal Medulla Attenuated Salt-sensitive Hypertension in Dahl S Rat

Hypertension ◽  
2012 ◽  
Vol 60 (suppl_1) ◽  
Author(s):  
Junping Hu ◽  
Qing Zhu ◽  
Wei-Qing Han ◽  
Pin-Lan Li ◽  
Ningjun Li
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Stem Cell ◽  
Control Cell ◽  
Renal Medulla ◽  
High Salt ◽  
Health Science ◽  
Stem Cell Markers ◽  
Cell Dysfunction ◽  
Salt Sensitive Hypertension

Transplantation of mesenchymal stem cells (MSCs) has been employed as a therapeutic strategy for many different diseases. We have recently shown that there is a stem cell dysfunction in the renal medulla that may contribute to the development of salt-sensitive hypertension in Dahl S rats. The present study tested the hypothesis that transplantation of MSCs into the renal medulla improves salt-sensitive hypertension in Dahl S rats. Rat adult MSCs were obtained from Texas A&M Health Science Center, ex-vivo expanded and infused (5 million cells) into the renal medulla in uninephrectomized Dahl S rats, which were then treated with low salt (LS, 0.4% NaCl) or high salt (HS, 8% NaCl) diet for 10 days. Results showed that the mRNA levels of stem cell markers CD133 and CD90 were increased by 60% and 70%, respectively, in the renal medulla in MSC-treated rats compared with control cell-treated rats. HS challenge increased mean arterial blood pressure in control cell-treated animals (from 113.9 ± 3.4 to 153.5 ± 4.8 mmHg), which was significantly attenuated in MSC-treated animals (from 114.1 ± 3.5 to 131.3 ± 2.5 mmHg). Meanwhile, ELISA analysis showed that the levels of pro-inflammatory cytokine interleukin-1β in the renal medulla were remarkably increased in HS-treated rats compared with LS-treated rats, which was blocked in MSC-treated rats (1.81 ± 0.18 ng/mg protein in LS group, 2.84 ± 0.57 in HS +control cell and 1.83 ± 0.35 in HS+MSC). Furthermore, immunostaining showed that the significant increase in immune cell (CD43+) infiltration into the renal medulla in HS control rats was reduced in HS+MSC rats. These results suggest that correction of stem cell dysfunction in the renal medulla attenuated inflammation in this kidney region after HS challenge and improved high salt-induced hypertension in Dahls S rats, which may serve as a therapeutic approach for salt-sensitive hypertension (supported by NIH grant HL89563 and HL106042)

scholarly journals Infusion of Valproic Acid Into the Renal Medulla Activates Stem Cell Population and Attenuates Salt-Sensitive Hypertension in Dahl S Rats

2017 ◽  
Vol 42 (3) ◽  
pp. 1264-1273
Author(s):  
Zhengchao Wang ◽  
Qing Zhu ◽  
Weili Wang ◽  
Fan Yi ◽  
Pin-Lan Li ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Valproic Acid ◽  
Stem Cell ◽  
Cell Function ◽  
Renal Medulla ◽  
High Salt ◽  
Stem Cell Marker ◽  
Cell Marker ◽  
Salt Sensitive Hypertension ◽  
Proinflammatory Factors

Background: Our previous study has detected a stem cell deficiency in the renal medulla in Dahl salt-sensitive (S) rats. This study determined whether infusion of valproic acid (VA), an agent known to stimulate the stem cell function, attenuated salt-sensitive hypertension in Dahl S rats. Methods: Uninephrectomized Dahl S rats were infused with vehicle or VA (50mg/kg/d) into the renal medulla and fed with a low (LS) or high salt diet (HS). Stem cell marker and number were analyzed by immunohistochemistry, Real-time RT-PCR and Western blot. Sodium excretion and blood pressure were measured. Results: VA significantly increased the mRNA and protein levels of FGF2, a stem cell niche factor, and CD133, a stem cell marker. The number of CD133+ cells was significantly increased in the renal medulla in VA-treated rats. Meanwhile, high salt-induced increases in the mRNA level of proinflammatory factors interleukin-1β and interleukin-6 were blocked in VA-treated rats. Functionally, sodium excretion in response to the blood pressure increase and acute sodium loading was significantly enhanced, sodium retention attenuated, high salt-induced increase of blood pressure reduced in VA-treated rats. Conclusion: Activation of stem cell function by VA inhibits the activation of proinflammatory factors and attenuates salt-sensitive hypertension in Dahl S rats.

scholarly journals Renal medullary 11β-hydroxysteroid dehydrogenase type 1 in Dahl salt-sensitive hypertension

2008 ◽  
Vol 36 (1) ◽  
pp. 52-58 ◽  
Author(s):  
Yong Liu ◽  
Ravinder J. Singh ◽  
Kristie Usa ◽  
Brian C. Netzel ◽  
Mingyu Liang
Keyword(s):  
Blood Pressure ◽  
Urinary Excretion ◽  
Molecular Mechanisms ◽  
Renal Medulla ◽  
Hydroxysteroid Dehydrogenase ◽  
Induced Hypertension ◽  
Intensive Investigation ◽  
Salt Sensitive Hypertension ◽  
Interfering Rna

The Dahl salt-sensitive rat is a widely used model of human salt-sensitive forms of hypertension. The kidney plays an important role in the pathogenesis of Dahl salt-sensitive hypertension, but the molecular mechanisms involved remain a subject of intensive investigation. Gene expression profiling studies suggested that 11β-hydroxysteroid dehydrogenase type 1 might be dysregulated in the renal medulla of Dahl salt-sensitive rats. Additional analysis confirmed that renal medullary expression of 11β-hydroxysteroid dehydrogenase type 1 was downregulated by a high-salt diet in SS-13BN rats, a consomic rat strain with reduced blood pressure salt sensitivity, but not in Dahl salt-sensitive rats. 11β-Hydroxysteroid dehydrogenase type 1 is known to convert inactive 11-dehydrocorticosterone to active corticosterone. The urinary corticosterone/11-dehydrocorticosterone ratio as well as urinary excretion of corticosterone was higher in Dahl salt-sensitive rats than in SS-13BN rats. Knockdown of renal medullary 11β-hydroxysteroid dehydrogenase type 1 with small-interfering RNA attenuated the early phase of salt-induced hypertension in Dahl salt-sensitive rats and reduced urinary excretion of corticosterone. Knockdown of 11β-hydroxysteroid dehydrogenase type 1 did not affect blood pressure in SS-13BN rats. Long-term attenuation of salt-induced hypertension was achieved with small hairpin RNA targeting renal medullary 11β-hydroxysteroid dehydrogenase type 1. In summary, we have demonstrated that suppression of 11β-hydroxysteroid dehydrogenase type 1 expression in the renal medulla attenuates salt-induced hypertension in Dahl salt-sensitive rats.

Insights into Dahl salt-sensitive hypertension revealed by temporal patterns of renal medullary gene expression

2003 ◽  
Vol 12 (3) ◽  
pp. 229-237 ◽  
Author(s):  
Mingyu Liang ◽  
Baozhi Yuan ◽  
Elizabeth Rute ◽  
Andrew S. Greene ◽  
Michael Olivier ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Renal Injury ◽  
Time Course ◽  
Expression Patterns ◽  
Renal Medulla ◽  
Temporal Patterns ◽  
Reference Distribution ◽  
Arterial Blood ◽  
Renal Tubular ◽  
Salt Sensitive Hypertension

Dahl salt-sensitive SS and consomic, salt-resistant SS-13BN/Mcw rats possess a highly similar genetic background but exhibit substantial differences in blood pressure salt sensitivity. We used cDNA microarrays to examine sequential changes of mRNA expression of ∼2,000 currently known rat genes in the renal medulla (a tissue critical for long-term blood pressure regulation) in SS and SS-13BN/Mcw rats in response to a high-salt diet (16 h, 3 days, or 2 wk). Differentially expressed genes in each between-group comparison were identified based on a threshold determined experimentally using a reference distribution that was constructed by comparing rats within the same group. A difference analysis of 54 microarrays identified 50 genes that exhibited the most distinct temporal patterns of expression between SS and SS-13BN/Mcw rats over the entire time course. Thirty of these genes could be linked to the regulation of arterial blood pressure or renal injury based on their known involvement in functional pathways such as renal tubular transport, metabolism of vasoactive substances, extracellular matrix formation, and apoptosis. Importantly, the majority of the 30 genes exhibited temporal expression patterns that would be expected to lower arterial pressure and reduce renal injury in SS-13BN/Mcw compared with SS rats. The phenotypic impact of the other 20 genes was less clear. These 50 genes are widely distributed on chromosome 13 and several other chromosomes. This suggested that primary genetic defects, although important, are unlikely to be solely responsible for the full manifestation of this type of hypertension and associated injury phenotypes. In summary, the results of this study identified a number of pathways potentially important for the amelioration of hypertension and renal injury in SS-13BN/Mcw rats, and these results generated a series of testable hypotheses related to the role of the renal medulla in the complex mechanism of salt-sensitive hypertension.

Stem Cell Defect in Ubiquitin-Green Fluorescent Protein Mice Facilitates Engraftment of Lymphoid-Primed Hematopoietic Stem Cells

Stem Cells ◽  
2018 ◽  
Vol 36 (8) ◽  
pp. 1237-1248
Author(s):  
Kateřina Faltusová ◽  
Katarína Szikszai ◽  
Martin Molík ◽  
Jana Linhartová ◽  
Petr Páral ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Green Fluorescent Protein ◽  
Hematopoietic Stem Cells ◽  
Fluorescent Protein ◽  
Hematopoietic Stem ◽  
Green Fluorescent ◽  
Cell Defect

scholarly journals Incomplete restoration of Mpl expression in the mpl−/− mouse produces partial correction of the stem cell–repopulating defect and paradoxical thrombocytosis

Blood ◽  
2009 ◽  
Vol 113 (8) ◽  
pp. 1778-1785 ◽  
Author(s):  
Brian J. Lannutti ◽  
Angela Epp ◽  
Jacqueline Roy ◽  
Junmei Chen ◽  
Neil C. Josephson
Keyword(s):  
Stem Cell ◽  
Elevated Plasma ◽  
Platelet Production ◽  
Ectopic Gene Expression ◽  
Unexpected Consequence ◽  
Kinase Phosphorylation ◽  
Bone Marrow Chimeras ◽  
Partial Correction ◽  
Cell Defect ◽  
Expression And Activity

Abstract Expression of Mpl is restricted to hematopoietic cells in the megakaryocyte lineage and to undifferentiated progenitors, where it initiates critical cell survival and proliferation signals after stimulation by its ligand, thrombopoietin (TPO). As a result, a deficiency in Mpl function in patients with congenital amegakaryocytic thrombocytopenia (CAMT) and in mpl−/− mice produces profound thrombocytopenia and a severe stem cell–repopulating defect. Gene therapy has the potential to correct the hematopoietic defects of CAMT by ectopic gene expression that restores normal Mpl receptor activity. We rescued the mpl−/− mouse with a transgenic vector expressing mpl from the promoter elements of the 2-kb region of DNA just proximal to the natural gene start site. Transgene rescued mice exhibit thrombocytosis but only partial correction of the stem cell defect. Furthermore, they show very low-level expression of Mpl on platelets and megakaryocytes, and the transgene-rescued megakaryocytes exhibit diminished TPO-dependent kinase phosphorylation and reduced platelet production in bone marrow chimeras. Thrombocytosis is an unexpected consequence of reduced Mpl expression and activity. However, impaired TPO homeostasis in the transgene-rescued mice produces elevated plasma TPO levels, which serves as an unchecked stimulus to drive the observed excessive megakaryocytopoiesis.

scholarly journals Interactions between 11β-hydroxysteroid dehydrogenase and COX-2 in kidney

2005 ◽  
Vol 288 (6) ◽  
pp. R1767-R1773 ◽  
Author(s):  
Bing Yao ◽  
Raymond C. Harris ◽  
Ming-Zhi Zhang
Keyword(s):  
Blood Pressure ◽  
Renal Medulla ◽  
Hydroxysteroid Dehydrogenase ◽  
High Salt ◽  
Adult Rats ◽  
Water Excretion ◽  
Suckling Rats ◽  
Apparent Mineralocorticoid Excess ◽  
Cox 2 ◽  
Salt Sensitive Hypertension

The syndrome of apparent mineralocorticoid excess (SAME) is an autosomal recessive form of salt-sensitive hypertension caused by deficiency of the kidney type 2 11β-hydroxysteroid dehydrogenase (11βHSD2). In this disorder, cortisol is not inactivated by 11βHSD2, occupies mineralocorticoid receptors (MRs), and causes excessive sodium retention and hypertension. In renal medulla, prostaglandins derived from cyclooxygenase-2 (COX-2) stimulate sodium and water excretion, and renal medullary COX-2 expression increases after mineralocorticoid administration. We investigated whether medullary COX-2 also increases in rats with 11βHSD2 inhibition and examined its possible role in the development of hypertension. 11βHSD2 inhibition increased medullary and decreased cortical COX-2 expression in adult rats and induced high blood pressure in high-salt-treated rats. COX-2 inhibition had no effect on blood pressure in control animals but further increased blood pressure in high-salt-treated rats with 11βHSD2 inhibition. COX-1 inhibition had no effect on blood pressure in either control or experimental animals. 11βHSD2 inhibition also led to medullary COX-2 increase and cortical COX-2 decrease in weaning rats, primarily through activation of MRs. In the suckling rats, medullary COX-2 expression was very low, consistent with a urinary concentrating defect. 11βHSD2 inhibition had no effect on either cortical or medullary COX-2 expression in the suckling rats, consistent with low levels of circulating corticosterone in these animals. These data indicate that COX-2 plays a modulating role in the development of hypertension due to 11βHSD2 deficiency and that 11βHSD2 regulates renal COX-2 expression by preventing glucocorticoid access to MRs during postnatal development.

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