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Scientific Reports Nov 2022Development of the renal medulla continues after birth to form mature renal papilla and obtain urine-concentrating ability. Here, we found that a small GTPase, Rac1,...
Development of the renal medulla continues after birth to form mature renal papilla and obtain urine-concentrating ability. Here, we found that a small GTPase, Rac1, plays a critical role in the postnatal development of renal papilla. Mice with distal tubule-specific deletion of Rac1 reached adulthood but showed polydipsia and polyuria with an impaired ability to concentrate urine. The elongation of renal papilla that occurs in the first weeks after birth was impaired in the Rac1-deficient infants, resulting in shortening and damage of the renal papilla. Moreover, the osmoprotective signaling mediated by nuclear factor of activated T cells 5, which is a key molecule of osmotic response to osmotic stress in renal medulla, was significantly impaired in the kidneys of the Rac1-deficient infants. These results demonstrate that Rac1 plays an important role in the development of renal papilla in the postnatal period, and suggested a potential link between Rac1 and osmotic response.
Topics: Mice; Animals; Kidney Medulla; Kidney; Signal Transduction
PubMed: 36434091
DOI: 10.1038/s41598-022-24462-5 -
Endokrynologia Polska 2013Thyroid hormone disorders in patients with chronic kidney disease (CKD) are a result of impaired conversion of T4 to T3. The importance of kidneys in thyroid hormones...
INTRODUCTION
Thyroid hormone disorders in patients with chronic kidney disease (CKD) are a result of impaired conversion of T4 to T3. The importance of kidneys in thyroid hormones conversion is not fully understood. The activities of different types of iodothyronine deiodinases in the kidney structures have not been determined yet. The aim of this study was to determine the activity of deiodinase type 1 (D1) and type 2 (D2) in renal cortex and medulla in renal cancer patients.
MATERIAL AND METHODS
Samples of renal cortex and medulla (ten patients) or renal cortex alone (13 patients) were taken from kidneys resected because of malignant cancer, from a site opposite to the cancer. Resections were performed in the 23 patients (seven female and 16 male) who were 52-82 years old. The material was stored at -72 oC.
RESULTS
Activity of D1 in renal cortex was 3.785 ± 2.041 fmol 125I/mg protein/minute and activity of D2 was 0.236 ± 0.125 fmol 125I/mg protein/minute. There was a strong positive correlation between D1 and D2 activities in renal cortex (r = 0.890, p 〈 0.001). Activity of D1 in renal medulla was 2.157 ± 2.176 fmol 125I/mg protein/minute, and activity of D2 was 0.168 ± 0.095 fmol 125I/mg protein/minute. A positive correlation between D1 and D2 in renal medulla (r = 0.661, p = 0.038) was observed as well. Activities of D1 in cortex and medulla were strongly and positively associated (r = 0.794, p = 0.006), whereas there was no correlation between the activities of D2 in cortex and medulla (r = 0.224, p = 0.553).
CONCLUSIONS
Results presented in this study suggest that both cortical and medullary D1 and D2 may be involved in thyroid hormone metabolism. This finding could be of clinical relevance in patients with impaired renal function.
Topics: Aged; Aged, 80 and over; Female; Humans; Iodide Peroxidase; Kidney Cortex; Kidney Medulla; Kidney Neoplasms; Male; Middle Aged; Statistics as Topic
PubMed: 23873420
DOI: No ID Found -
American Journal of Physiology.... Jun 2003The unique role of nitric oxide (NO) in the regulation of renal medullary function is supported by the evidence summarized in this review. The impact of reduced... (Review)
Review
The unique role of nitric oxide (NO) in the regulation of renal medullary function is supported by the evidence summarized in this review. The impact of reduced production of NO within the renal medulla on the delivery of blood to the medulla and on the long-term regulation of sodium excretion and blood pressure is described. It is evident that medullary NO production serves as an important counterregulatory factor to buffer vasoconstrictor hormone-induced reduction of medullary blood flow and tissue oxygen levels. When NO synthase (NOS) activity is reduced within the renal medulla, either pharmacologically or genetically [Dahl salt-sensitive (S) rats], a super sensitivity to vasoconstrictors develops with ensuing hypertension. Reduced NO production may also result from reduced cellular uptake of l-arginine in the medullary tissue, resulting in hypertension. It is concluded that NO production in the renal medulla plays a very important role in sodium and water homeostasis and the long-term control of arterial pressure.
Topics: Animals; Blood Pressure; Humans; Kidney Medulla; Nitric Oxide; Renal Circulation; Vasoconstriction
PubMed: 12736168
DOI: 10.1152/ajpregu.00701.2002 -
Acta Physiologica (Oxford, England) Feb 2013Regulation of medullary blood flow (MBF) is essential in maintaining normal kidney function. Blood flow to the medulla is supplied by the descending vasa recta (DVR),... (Review)
Review
Regulation of medullary blood flow (MBF) is essential in maintaining normal kidney function. Blood flow to the medulla is supplied by the descending vasa recta (DVR), which arise from the efferent arterioles of juxtamedullary glomeruli. DVR are composed of a continuous endothelium, intercalated with smooth muscle-like cells called pericytes. Pericytes have been shown to alter the diameter of isolated and in situ DVR in response to vasoactive stimuli that are transmitted via a network of autocrine and paracrine signalling pathways. Vasoactive stimuli can be released by neighbouring tubular epithelial, endothelial, red blood cells and neuronal cells in response to changes in NaCl transport and oxygen tension. The experimentally described sensitivity of pericytes to these stimuli strongly suggests their leading role in the phenomenon of MBF autoregulation. Because the debate on autoregulation of MBF fervently continues, we discuss the evidence favouring a physiological role for pericytes in the regulation of MBF and describe their potential role in tubulo-vascular cross-talk in this region of the kidney. Our review also considers current methods used to explore pericyte activity and function in the renal medulla.
Topics: Animals; Humans; Kidney Medulla; Pericytes; Renal Circulation
PubMed: 23126245
DOI: 10.1111/apha.12026 -
BMC Urology Nov 2021Nephrocalcinosis is often asymptomatic but can manifest with renal colic or hematuria. There is no reported association between nephrocalcinosis and renal vascular...
BACKGROUND
Nephrocalcinosis is often asymptomatic but can manifest with renal colic or hematuria. There is no reported association between nephrocalcinosis and renal vascular malformations, which may also be a source of hematuria. We herein present a case of a patient with hematuria related to nephrocalcinosis and renal papillary varicosities. These varicosities were diagnosed and successfully treated with flexible ureteroscopy and laser fulguration.
CASE PRESENTATION
A 24-year-old female with a history of epilepsy (on zonisamide), recent uncomplicated pregnancy, and new diagnosis of nephrocalcinosis presented with right flank pain and intermittent gross hematuria. Imaging revealed intermittent right sided hydronephrosis. A cystoscopy identified hematuria from the right ureteral orifice. Diagnostic flexible ureteroscopy revealed numerous intrapapillary renal stones and varicose veins of several renal papillae. A 200 μm holmium laser fiber was used to unroof these stones and fulgurate the varicosities with resolution of her symptoms for several months. She later presented with left-sided symptoms and underwent left ureteroscopy with similar findings and identical successful treatment.
CONCLUSION
Unilateral hematuria from discrete vascular lesions of the renal collecting system may be obscured by other benign co-existing conditions, such as nephrocalcinosis and nephrolithiasis. Although a simultaneous presentation is rare, flexible ureteroscopy with laser fulguration offers an ideal diagnostic and therapeutic modality for these concurrent conditions if symptoms arise.
Topics: Female; Hematuria; Humans; Kidney Calculi; Kidney Medulla; Laser Coagulation; Nephrocalcinosis; Ureteroscopy; Varicose Veins; Young Adult
PubMed: 34844581
DOI: 10.1186/s12894-021-00931-3 -
Genomics May 2020Camels as a sort of animal long living in desert have evolved stress-resistance characteristics to adapt to environment with high temperature and water shortage...
Camels as a sort of animal long living in desert have evolved stress-resistance characteristics to adapt to environment with high temperature and water shortage environment. However, the research of non-coding RNA (ncRNA)-mediated molecular regulation about how camel responds to arid condition in post-transcriptional regulation level is deficient. Under water-deprivation stress, by RNA-sequencing of camel renal medulla associated with regulating water metabolism, we detected significantly differential 575 alternative splicing events (ASEs) and 17 mRNAs, 26 miRNAs and 0 lncRNA. The down-regulated ACLY and LOC105061856, up-regulated PCBP2 and miR-195 potentially targeting LOC105061856 and PCBP2 mRNA were selected as candidate resistance-related genes. In quantitative experiment, the expression level of above four genes was consistent with RNA-seq data by qRT-PCR. The suppressive cell dehydration with down-regulated ACLY, inhibitive aerobic respiration with down-regulated LOC105061856 targeted by miR-195 and strong anti-oxidative capability with PCBP2 aimed by miR-195 may be regulatory modes of camel renal medulla adapting to water-deprivation condition.
Topics: Alternative Splicing; Animals; Camelus; Dehydration; Droughts; Female; Gene Expression Regulation; Kidney Medulla; MicroRNAs; RNA, Long Noncoding; RNA, Messenger
PubMed: 32070763
DOI: 10.1016/j.ygeno.2020.02.014 -
Physiological Reviews Oct 2007Cells in the renal inner medulla are normally exposed to extraordinarily high levels of NaCl and urea. The osmotic stress causes numerous perturbations because of the... (Review)
Review
Cells in the renal inner medulla are normally exposed to extraordinarily high levels of NaCl and urea. The osmotic stress causes numerous perturbations because of the hypertonic effect of high NaCl and the direct denaturation of cellular macromolecules by high urea. High NaCl and urea elevate reactive oxygen species, cause cytoskeletal rearrangement, inhibit DNA replication and transcription, inhibit translation, depolarize mitochondria, and damage DNA and proteins. Nevertheless, cells can accommodate by changes that include accumulation of organic osmolytes and increased expression of heat shock proteins. Failure to accommodate results in cell death by apoptosis. Although the adapted cells survive and function, many of the original perturbations persist, and even contribute to signaling the adaptive responses. This review addresses both the perturbing effects of high NaCl and urea and the adaptive responses. We speculate on the sensors of osmolality and document the multiple pathways that signal activation of the transcription factor TonEBP/OREBP, which directs many aspects of adaptation. The facts that numerous cellular functions are altered by hyperosmolality and remain so, even after adaptation, indicate that both the effects of hyperosmolality and adaptation to it involve profound alterations of the state of the cells.
Topics: Animals; Humans; Hypertonic Solutions; Kidney Medulla; NFATC Transcription Factors; Osmotic Pressure; Sodium Chloride; Urea
PubMed: 17928589
DOI: 10.1152/physrev.00056.2006 -
Kidney International. Supplement Sep 1998Vasoactive peptides regulate renal medullary microcirculation and tubular function, but the localization of their receptors and mechanisms of actions are currently... (Review)
Review
Vasoactive peptides regulate renal medullary microcirculation and tubular function, but the localization of their receptors and mechanisms of actions are currently unknown. Using electron microscopic autoradiography, we have mapped the receptors for angiotensin II (Ang II [AT1 and AT2]), endothelin (ET(A) and ET(B)), and bradykinin (B2) in the rat renal medulla. Although these peptide receptors show distinct vascular and tubular distributions, they overlap strikingly in renomedullary interstitial cells (RMICs) of the inner stripe and the papilla. Using reverse transcription-polymerase chain reaction (RT-PCR) and Southern analysis, mRNAs for AT1A, ET(A), and B2 receptors were detected in cultured adult RMICs. Ang II increases intracellular inositol 1,4,5-triphosphate (IP3) and [Ca2+]i and stimulates [3H]thymidine incorporation and extracellular matrix (ECM) synthesis via AT1A receptors. Endothelin and bradykinin also stimulate cell proliferation and ECM synthesis in RMICs through ET(A) and B2 receptors, respectively, but the actions of endothelin are modulated by concurrent nitric oxide production. By contrast, AT2 receptor mRNA was detected only in embryonic RMICs, in which Ang II inhibits cell proliferation through this receptor. These results suggest that multiple vasoactive peptides may interact with RMICs to exert endocrine and/or paracrine influences on renal medullary microcirculation and tubular function.
Topics: Animals; Kidney Medulla; Receptor, Bradykinin B2; Receptors, Angiotensin; Receptors, Bradykinin; Receptors, Endothelin
PubMed: 9736248
DOI: 10.1046/j.1523-1755.1998.06705.x -
Kidney International Oct 2002Western blotting has previously been used to identify changes in protein expression in renal tissue. However, only a few proteins can be studied in each experiment by...
BACKGROUND
Western blotting has previously been used to identify changes in protein expression in renal tissue. However, only a few proteins can be studied in each experiment by Western blot. We have used proteomic tools to construct protein maps of rat kidney cortex and medulla.
METHODS
Expression of proteins was determined by silver stain after two-dimensional polyacrylamide gel electrophoresis (2D-PAGE). Protein spots were excised and digested with trypsin. Peptide masses were identified by MALDI-TOF mass spectrometry. The Mascot search engine was used to analyze the peptide masses and identify the proteins.
RESULTS
Seventy-two proteins were identified (54 unique proteins) out of approximately 1000 spots visualized on each gel. Most of the spots were expressed both in cortex and medulla. Of the identified proteins, three were expressed only in medulla and one only in cortex. Nine proteins were expressed in both regions but to a greater extent in cortex and three proteins were expressed more in medulla. Differential expression was confirmed for three proteins by Western blot.
CONCLUSIONS
A large group of proteins and their relative expression levels from cortical and medullary portions of rat kidneys were found. Sixteen proteins are differentially expressed. Proteomics can be used to identify differential expression of proteins in the kidney on a large scale. Proteomics should be useful to detect changes in renal protein expression in response to a large range of physiological and pathophysiological stimuli.
Topics: Animals; Electrophoresis, Gel, Two-Dimensional; Kidney Cortex; Kidney Medulla; Proteins; Proteomics; Rats; Rats, Sprague-Dawley; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
PubMed: 12234301
DOI: 10.1111/j.1523-1755.2002.kid588.x -
Acta Physiologica (Oxford, England) Jul 2011This is an informal personal review of the development over time of my ideas about the concentrating mechanism of the mammalian renal papilla. It had been observed that... (Review)
Review
This is an informal personal review of the development over time of my ideas about the concentrating mechanism of the mammalian renal papilla. It had been observed that animals with a need to produce a concentrated urine have a long renal papilla. I saw the function of the long papilla in desert rodents as an elongation of the counter-current concentrating mechanism of the inner medulla. This model led me to overlook contrary evidence. For example, in many experiments, the final urine has a higher osmolality than that of the tissue at the tip of the papilla. In addition, we had observations of the peristalsis of the renal pelvis surrounding the papilla. The urine concentration falls if the peristalsis is stopped. I was wrong; together, these lines of evidence show that the renal papilla is not just an elongation of the inner medulla. We are left without a full explanation of the concentrating mechanism of the mammalian renal papilla. It is hoped that other researchers will tackle this interesting problem.
Topics: Animals; Kidney Concentrating Ability; Kidney Medulla; Kidney Pelvis; Osmolar Concentration; Peristalsis; Urea; Urine
PubMed: 21281458
DOI: 10.1111/j.1748-1716.2011.02261.x