scholarly journals Diverse Cell Populations Involved in Regeneration of Renal Tubular Epithelium following Acute Kidney Injury

2015 ◽  
Vol 2015 ◽  
pp. 1-8 ◽  
Author(s):  
Akito Maeshima ◽  
Shunsuke Takahashi ◽  
Masao Nakasatomi ◽  
Yoshihisa Nojima
Keyword(s):  
Stem Cell ◽  
Kidney Diseases ◽  
Kidney Injury ◽  
Cell Populations ◽  
Renal Tubules ◽  
Stem Cell Markers ◽  
Tubular Epithelium ◽  
Tubular Cells ◽  
Renal Tubular Epithelium ◽  
Renal Tubular

Renal tubular epithelium has the capacity to regenerate, repair, and reepithelialize in response to a variety of insults. Previous studies with several kidney injury models demonstrated that various growth factors, transcription factors, and extracellular matrices are involved in this process. Surviving tubular cells actively proliferate, migrate, and differentiate in the kidney regeneration process after injury, and some cells express putative stem cell markers or possess stem cell properties. Using fate mapping techniques, bone marrow-derived cells and endothelial progenitor cells have been shown to transdifferentiate into tubular components in vivo or ex vivo. Similarly, it has been demonstrated that, during tubular cell regeneration, several inflammatory cell populations migrate, assemble around tubular cells, and interact with tubular cells during the repair of tubular epithelium. In this review, we describe recent advances in understanding the regeneration mechanisms of renal tubules, particularly the characteristics of various cell populations contributing to tubular regeneration, and highlight the targets for the development of regenerative medicine for treating kidney diseases in humans.

Excretion of ammonia injected into renal artery

1962 ◽  
Vol 203 (1) ◽  
pp. 11-14 ◽  
Author(s):  
Sulamita Balagura ◽  
Robert F. Pitts
Keyword(s):  
Renal Artery ◽  
Maximum Rate ◽  
Time Course ◽  
Hydrogen Ion ◽  
Tubular Epithelium ◽  
Free Base ◽  
Ion Concentrations ◽  
Tubular Cells ◽  
Renal Tubular Epithelium ◽  
Renal Tubular

Certain characteristics of the ammonia secretory mechanism in the dog have been studied by the method of Chinard. Ammonium chloride or acetate and creatinine were rapidly injected into one renal artery and a series of urine samples were collected separately from the two ureters. In acidosis, injected ammonia appears in the urine earlier than does creatinine, indicating that some fraction enters the tubule from the blood downstream from the glomerulus. The maximum rate of excretion of ammonia relative to the dose administered is usually less than that of creatinine, indicating that filtered ammonia is in part reabsorbed from the tubular urine. Finally, the excretion of ammonia is much prolonged relative to creatinine, indicating that it continues to be added to the tubular urine from cellular stores built up from both filtrate and peritubular blood. In alkalosis, the time course of excretion of creatinine is unchanged from that observed in acidosis. However, the excretion of ammonia is abolished. That which enters the tubule in the filtrate is completely reabsorbed. These data are consistent with the view that ammonia diffuses freely in both directions across the renal tubular epithelium as free base and distributes among tubular urine, tubular cells, and peritubular blood in accordance with their respective hydrogen ion concentrations.

scholarly journals Inhibition of HDAC6 protects against rhabdomyolysis-induced acute kidney injury

2017 ◽  
Vol 312 (3) ◽  
pp. F502-F515 ◽  
Author(s):  
Yingfeng Shi ◽  
Liuqing Xu ◽  
Jinhua Tang ◽  
Lu Fang ◽  
Shuchen Ma ◽  
...  
Keyword(s):  
Acute Kidney Injury ◽  
Therapeutic Potential ◽  
Apoptotic Cell ◽  
Kidney Injury ◽  
Acute Injury ◽  
Tubular Damage ◽  
Renal Tubules ◽  
Tubular Cells ◽  
Renal Tubular Cells ◽  
Renal Tubular

Histone deacetylase 6 (HDAC6) inhibition has been reported to protect against ischemic stroke and prolong survival after sepsis in animal models. However, it remains unknown whether HDAC6 inhibition offers a renoprotective effect after acute kidney injury (AKI). In this study, we examined the effect of tubastatin A (TA), a highly selective inhibitor of HDAC6, on AKI in a murine model of glycerol (GL) injection-induced rhabdomyolysis. Following GL injection, the mice developed severe acute tubular injury as indicated by renal dysfunction; expression of neutrophil gelatinase-associated lipocalin (NGAL), an injury marker of renal tubules; and an increase of TdT-mediated dUTP nick-end labeling (TUNEL)-positive tubular cells. These changes were companied by increased HDAC6 expression in the cytoplasm of renal tubular cells. Administration of TA significantly reduced serum creatinine and blood urea nitrogen levels as well as attenuated renal tubular damage in injured kidneys. HDAC6 inhibition also resulted in decreased expression of NGAL, reduced apoptotic cell, and inactivated caspase-3 in the kidney after acute injury. Moreover, injury to the kidney increased phosphorylation of nuclear factor (NF)-κB and expression of multiple cytokines/chemokines including tumor necrotic factor-α and interleukin-6 and monocyte chemoattractant protein-1, as well as macrophage infiltration. Treatment with TA attenuated all those responses. Finally, HDAC6 inhibition reduced the level of oxidative stress by suppressing malondialdehyde (MDA) and preserving expression of superoxide dismutase (SOD) in the injured kidney. Collectively, these data indicate that HDAC6 contributes to the pathogenesis of rhabdomyolysis-induced AKI and suggest that HDAC6 inhibitors have therapeutic potential for AKI treatment.

scholarly journals PARK7 Protects Against Chronic Kidney Injury and Renal Fibrosis by Inducing SOD2 to Reduce Oxidative Stress

2021 ◽  
Vol 12 ◽  
Author(s):  
Lijun Yin ◽  
Honglin Li ◽  
Zhiwen Liu ◽  
Wenwen Wu ◽  
Juan Cai ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Cell Apoptosis ◽  
Renal Fibrosis ◽  
Kidney Diseases ◽  
Kidney Injury ◽  
Ros Production ◽  
Tubular Cells ◽  
Renal Tubular Cells ◽  
Chronic Kidney Injury ◽  
Renal Tubular

Renal fibrosis is the final common pathway to chronic kidney diseases regardless of etiology. Parkinson disease protein 7 (PARK7) is a multifunctional protein involved in various cellular processes, but its pathophysiological role in kidneys remain largely unknown. Here, we have determined the role of PARK7 in renal fibrosis and have further elucidated the underlying mechanisms by using the in vivo mouse model of unilateral ureteric obstruction (UUO) and the in vitro model of transforming growth factor-b (TGFB1) treatment of cultured kidney proximal tubular cells. PARK7 decreased markedly in atrophic kidney tubules in UUO mice, and Park7 deficiency aggravated UUO-induced renal fibrosis, tubular cell apoptosis, ROS production and inflammation. In vitro, TGFB1 treatment induced fibrotic changes in renal tubular cells, which was accompanied by alterations of PARK7. Park7 knockdown exacerbated TGFB1-induced fibrotic changes, cell apoptosis and ROS production, whereas Park7 overexpression or treatment with ND-13 (a PARK7-derived peptide) attenuated these TGFB1-induced changes. Mechanistically, PARK7 translocated into the nucleus of renal tubular cells following TGFB1 treatment or UUO, where it induced the expression of SOD2, an antioxidant enzyme. Taken together, these results indicate that PARK7 protects against chronic kidney injury and renal fibrosis by inducing SOD2 to reduce oxidative stress in tubular cells.

CO2 equilibria in renal tissue

1980 ◽  
Vol 239 (4) ◽  
pp. F307-F318 ◽  
Author(s):  
Gerhard Malnic
Keyword(s):  
Carbonic Acid ◽  
Water Layer ◽  
Renal Tissue ◽  
Buffer System ◽  
Renal Tubules ◽  
Tubular Epithelium ◽  
Renal Tubular Epithelium ◽  
Arterial Blood ◽  
Disequilibrium Ph ◽  
Renal Tubular

Disequilibrium situations within the bicarbonate/CO2 buffer system have been observed in the kidney. On the one hand, a Pco2 difference between final urine and arterial blood has been detected. On the other, a disequilibrium pH was found in cortical renal tubules and attributed to either increased carbonic acid concentrations or to Pco2 levels above those of arterial blood. Recent methodological developments have yielded better insight into these disequilibrium situations. They include, besides the use of pH microelectrodes, the introduction of microcalorimetric total CO2 determinations and Pco2 microelectrodes. There is agreement concerning the finding of a Pco2 10–40 mmHg above that in arterial blood in renal cortical tubules; however, stellate vessel Pco2 equal to tubular Pco2 was found by only one group of investigators. According to their view, diffusion equilibrium exists between all cortical structures, a finding disputed by others using a similar methodology. CO2 permeability of tubular epithelium is also still controversial, with values ranging from one-half (microcalorimetric method) to one-twentieth (pH-equilibration method) of an equivalent water layer having been reported. Two positions emerge on the basis of recent experimental results: the existence of very high permeability to CO2 and consequent diffusion equilibrium in renal cortex, and the occurrence of CO2 diffusion limitation leading to the establishment of finite Pco2 gradients across renal tubular epithelium. disequilibrium pH; CO2 permeability; tubular Pco2; CO22 fluxes; carbonic anhydrase

scholarly journals III. TOLERANCE FOR MERCURY POISONING INCREASED BY FREQUENT HEMOGLOBIN INJECTIONS

1932 ◽  
Vol 55 (4) ◽  
pp. 627-635 ◽  
Author(s):  
William H. Havill ◽  
John A. Lichty ◽  
George H. Whipple
Keyword(s):  
Functional Disability ◽  
Lethal Dose ◽  
Severe Reaction ◽  
Renal Tubules ◽  
Tubular Epithelium ◽  
Mercury Poisoning ◽  
Renal Tubular Epithelium ◽  
Rest Periods ◽  
Renal Tubular ◽  
Lethal Doses

Frequent injections of superthreshold amounts of dog hemoglobin will cause deposits of pigment material in the renal tubular epithelium. When this has happened this dog will survive minimal lethal doses of mercuric chloride with little evidence of renal injury. In fact some dogs will tolerate twice the minimal lethal dose without severe reaction. There is no evidence that continued injections of dog hemoglobin in these amounts will cause any injury or functional disability of the kidney. Rest periods will effect a disappearance of this pigment in the renal tubules.

Osteopontin expressed by renal tubular epithelium mediates interstitial monocyte infiltration in rats

2000 ◽  
Vol 278 (1) ◽  
pp. F110-F121 ◽  
Author(s):  
Hirokazu Okada ◽  
Kenshi Moriwaki ◽  
Raghuram Kalluri ◽  
Tsuneo Takenaka ◽  
Hiroe Imai ◽  
...  
Keyword(s):  
Target Genes ◽  
Renal Plasma Flow ◽  
Mrna Level ◽  
Antisense Oligodeoxynucleotide ◽  
Tubular Epithelium ◽  
Rt Pcr ◽  
Goodpasture Syndrome ◽  
Renal Tubular Epithelium ◽  
Protein Excretion ◽  
Renal Tubular

In this study, we have shown that intravenously administered antisense oligodeoxynucleotide (ODN) was demonstrated to be taken up by tubular epithelium, after which it blocked mRNA expression of target genes in normal and nephritic rats. Therefore, we injected osteopontin (OPN) antisense ODN to Goodpasture syndrome (GPS) rats every second day between days 27 and 35, the time when renal OPN expression increased and interstitial monocyte infiltration was aggravated. In parallel to blockade of tubular OPN expression, this treatment significantly attenuated monocyte infiltration and preserved renal plasma flow in GPS rats at day 37, compared with sense ODN-treated and untreated GPS rats. No significant changes were observed in OPN mRNA level by RT-PCR and histopathology of the glomeruli after ODN treatment, which was compatible with an absence of differences in the urinary protein excretion rate. In conclusion, OPN expressed by tubular epithelium played a pivotal role in mediating peritubular monocyte infiltration consequent to glomerular disease.

scholarly journals O7: APPARENT PATHOLOGICAL COMPLETE RESPONSE TO NEOADJUVANT THERAPY LEADS TO SELECTION OF TREATMENT RESISTANT CANCER STEM CELLS IN OESOPHAGEAL ADENOCARCINOMA

2021 ◽  
Vol 108 (Supplement_1) ◽  
Author(s):  
RC Walker ◽  
J Harrington ◽  
B Grace ◽  
M Lloyd ◽  
JP Byrne ◽  
...  
Keyword(s):  
Stem Cell ◽  
Cancer Cells ◽  
Neoadjuvant Therapy ◽  
Rna Sequencing ◽  
Pathological Complete Response ◽  
Complete Response ◽  
Oesophageal Adenocarcinoma ◽  
Cell Populations ◽  
Stem Cell Markers ◽  
Resistance To Therapy

Abstract Introduction In oesophageal adenocarcinoma with an apparent pathological complete response (pCR) to neoadjuvant therapy (NAT) there remains debate as to whether oesophagectomy is required. Single Cell RNA sequencing (scRNAseq) enables identification and characterisation of cell populations at higher resolution than diagnostic techniques. Method ScRNAseq was used to determine transcriptomic profiles of cell populations in 24 OAC tumours and 13 matched normal samples. Five were also analysed using bulk RNA sequencing and high-precision mass spectrometry proteomics. Immunohistochemistry (IHC) was used to validate pCR. Paired scRNAseq analysis of pre-and post-treatment specimens from three further patients was used to compare transcriptomic profiles before and after NAT. Cancer cells (CCs) were assigned a cancer stem cell (CSC) score curated from published gene sets. Result We analysed a total of 22,738 single cells forming 29 different cell phenotypes. In two samples with apparent pCR, IHC staining, bulk RNA sequencing and proteomics of post-treatment samples failed to identify CCs. ScRNAseq, conversely, revealed persistent CCs (12/978 and 45/774). Transcriptomic analysis identified upregulation of stem cell markers and high CSC scores in these cells. Conclusion We have shown that CCs persist beneath the lower detection limit of standard approaches in apparent pCR. These cells express marker genes and expression programs consistent with CSCs. CSCs are a critical subpopulation that drive tumour initiation, growth, invasion, metastasis and resistance to therapy. These gene expression programs are not enriched in non-responders and straight to surgery samples. Oesophagus sparing treatment algorithms in pCR may subject patients to unnecessary risk of progression. Take-home message Cancer cells remain within tumours after apparent complete pathological response. These cells express stem cell markers associated with resistance to therapy and cancer progression.

scholarly journals The intrinsic prostaglandin E2–EP4 system of the renal tubular epithelium limits the development of tubulointerstitial fibrosis in mice

2012 ◽  
Vol 82 (2) ◽  
pp. 158-171 ◽  
Author(s):  
Naoki Nakagawa ◽  
Koh-ichi Yuhki ◽  
Jun-ichi Kawabe ◽  
Takayuki Fujino ◽  
Osamu Takahata ◽  
...  
Keyword(s):  
Prostaglandin E2 ◽  
Tubulointerstitial Fibrosis ◽  
Tubular Epithelium ◽  
Renal Tubular Epithelium ◽  
Renal Tubular

scholarly journals Cystic Renal Neoplasia Following Conditional Inactivation of Apc in Mouse Renal Tubular Epithelium

2004 ◽  
Vol 280 (5) ◽  
pp. 3938-3945 ◽  
Author(s):  
Chao-Nan Qian ◽  
Jared Knol ◽  
Peter Igarashi ◽  
Fangming Lin ◽  
Uko Zylstra ◽  
...  
Keyword(s):  
Tubular Epithelium ◽  
Renal Tubular Epithelium ◽  
Conditional Inactivation ◽  
Renal Tubular ◽  
Renal Neoplasia
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