Acute kidney injury(AKI)is a significant global health issue with limited current treatment options.This study focused on the mechanism by which exosomes derived from bone marrow mesenchymal stem cells(BMSCs)promote r...Acute kidney injury(AKI)is a significant global health issue with limited current treatment options.This study focused on the mechanism by which exosomes derived from bone marrow mesenchymal stem cells(BMSCs)promote renal tubule regeneration in AKI through the regulation of the PTEN signaling pathway by miR-21.BMSCs were isolated and characterized,and their exosomes were purified.In vitro,renal tubular epithelial cell injury models were established,and the co-culture of exosomes and cells demonstrated enhanced cell proliferation and reduced apoptosis.In vivo,AKI animal models showed improved renal function and histopathological changes after exosome treatment.miR-21 was found to be upregulated in exosomes and recipient cells,targeting PTEN and activating the PI3K/AKT pathway.The signaling network also interacted with other pathways related to renal tubule regeneration.The study highlights the potential of exosome therapy for AKI and provides insights into the underlying molecular mechanisms,although further research is needed to address remaining challenges and translate these findings into clinical applications.展开更多
Acetaminophen is a drug used to treat many conditions as headache, muscle aches, arthritis, backache, toothache, and fever between others, but collateral effects of this drug are not well known yet. Here is tested its...Acetaminophen is a drug used to treat many conditions as headache, muscle aches, arthritis, backache, toothache, and fever between others, but collateral effects of this drug are not well known yet. Here is tested its effect on proximal tubule epithelium. Acetaminophen (APAP) at doses of 200, 500, 1000 and 1500 mg/Kg i.p. caused cell damage and changes in F-actin distribution in the proximal tubule of male Wistar rats. After 48 hours of treatment, the proximal tubule epithelium showed tumefaction and necrosis. Dose of 200 mg/kg decreased the F-actin and was observed a structure in patches in the basal cytoplasm of epithelial cells of the proximal tubule. This effect was increased depending on the administered dose. Dose of 1000 mg/kg produced the highest histological damage and changes in the actin cytoskeleton. Results of this study suggested that nephrotoxic damage produced by high doses of APAP included breakdown of cytoskeleton in proximal tubule epithelium.展开更多
Kidney disease is an escalating global health problem,for which the formulation of therapeutic approaches using stem cells has received increasing research attention.The complexity of kidney anatomy and function,which...Kidney disease is an escalating global health problem,for which the formulation of therapeutic approaches using stem cells has received increasing research attention.The complexity of kidney anatomy and function,which includes the diversity of renal cell types,poses formidable challenges in the identification of methods to generate replacement structures.Recent work using the zebrafish has revealed their high capacity to regenerate the integral working units of the kidney,known as nephrons,following acute injury.Here,we discuss these findings and explore the ways that zebrafish can be further utilized to gain a deeper molecular appreciation of renal stem cell biology,which may uncover important clues for regenerative medicine.展开更多
Acute tubular necrosis(ATN)induced by ischemia is the most common insult to donor kidneysdestined for trarsplantation.ATN results from sweling and subsequent damage to cells lining thelkidney tubules.In this study,we ...Acute tubular necrosis(ATN)induced by ischemia is the most common insult to donor kidneysdestined for trarsplantation.ATN results from sweling and subsequent damage to cells lining thelkidney tubules.In this study,we demonstrate the capability of optical coherence tomography(OcT)to image the renal microst ructures of living human donor kidneys and potentially providea measure to det ermine the extent of A TN.We also found that Doppler-based OCT(i.e.,DOCT)reveals renal blood flow dynamics that is another major factor which could relate to post-transplant renal finction.All OCT/DoCT oberva tions were performed in a noninvasive,sterileand timely manner on intact human kidneys both prior to(er vivo)and following(in vivo)theirtransplantation.Our results indicate that this imaging model provides transplant surgeons withan objective visualization of the transplant lidneys prior and immediately post transplantation.展开更多
Current dialysis systems are not perfect considering the low efficacy and cumbersome process of actual practice. To overcome these shortcomings, bioartificial kidneys using renal tubule cells and wearable dialysis are...Current dialysis systems are not perfect considering the low efficacy and cumbersome process of actual practice. To overcome these shortcomings, bioartificial kidneys using renal tubule cells and wearable dialysis are promising ESRD treatments available in the near future. Toward clinical application, however, there are so many obstacles for commercial use of them. In this review, current status of bioartificial kidneys such as the renal tubule cell assist device (RAD) and wearable dialysis devices is presented with the comparison to show the advantages and disadvantages.展开更多
950350 Improving lithium clearance——a methodfor measuring sodium delivery of tubule in human.WANG Huamin(王化民),et al.Nephrol Div,1stTeach Hosp,Beijing Med Univ.Chin J Nephrol 1994;10(6):326-328.Based on the method...950350 Improving lithium clearance——a methodfor measuring sodium delivery of tubule in human.WANG Huamin(王化民),et al.Nephrol Div,1stTeach Hosp,Beijing Med Univ.Chin J Nephrol 1994;10(6):326-328.Based on the method for lithium clearance,we ob-served the relationship between serum lithium concen-tration at the fouth hour in the test and the representa-tive serum lithium concentration,and verified that展开更多
The mechanism of how SARS-CoV-2 causes severe multi-organ failure is largely unknown. Acute kidney injury(AKI) is one of the frequent organ damage in severe COVID-19 patients. Previous studies have shown that human re...The mechanism of how SARS-CoV-2 causes severe multi-organ failure is largely unknown. Acute kidney injury(AKI) is one of the frequent organ damage in severe COVID-19 patients. Previous studies have shown that human renal tubule cells could be the potential host cells targeted by SARS-CoV-2. Traditional cancer cell lines or immortalized cell lines are genetically and phenotypically different from host cells. Animal models are widely used, but often fail to reflect a physiological and pathogenic status because of species tropisms. There is an unmet need for normal human epithelial cells for disease modeling. In this study, we successfully established long term cultures of normal human kidney proximal tubule epithelial cells(KPTECs) in 2 D and 3 D culture systems using conditional reprogramming(CR) and organoids techniques.These cells had the ability to differentiate and repair DNA damage, and showed no transforming property. Importantly, the CR KPTECs maintained lineage function with expression of specific transporters(SLC34 A3 and cubilin). They also expressed angiotensin-converting enzyme 2(ACE2), a receptor for SARS-CoV and SARS-CoV-2. In contrast, cancer cell line did not express endogenous SLC34 A3, cubilin and ACE2. Very interestingly, ACE2 expression was around twofold higher in 3 D organoids culture compared to that in 2 D CR culture condition. Pseudovirion assays demonstrated that SARS-CoV spike(S) protein was able to enter CR cells with luciferase reporter. This integrated 2 D CR and 3 D organoid cultures provide a physiological ex vivo model to study kidney functions, innate immune response of kidney cells to viruses, and a novel platform for drug discovery and safety evaluation.展开更多
文摘Acute kidney injury(AKI)is a significant global health issue with limited current treatment options.This study focused on the mechanism by which exosomes derived from bone marrow mesenchymal stem cells(BMSCs)promote renal tubule regeneration in AKI through the regulation of the PTEN signaling pathway by miR-21.BMSCs were isolated and characterized,and their exosomes were purified.In vitro,renal tubular epithelial cell injury models were established,and the co-culture of exosomes and cells demonstrated enhanced cell proliferation and reduced apoptosis.In vivo,AKI animal models showed improved renal function and histopathological changes after exosome treatment.miR-21 was found to be upregulated in exosomes and recipient cells,targeting PTEN and activating the PI3K/AKT pathway.The signaling network also interacted with other pathways related to renal tubule regeneration.The study highlights the potential of exosome therapy for AKI and provides insights into the underlying molecular mechanisms,although further research is needed to address remaining challenges and translate these findings into clinical applications.
文摘Acetaminophen is a drug used to treat many conditions as headache, muscle aches, arthritis, backache, toothache, and fever between others, but collateral effects of this drug are not well known yet. Here is tested its effect on proximal tubule epithelium. Acetaminophen (APAP) at doses of 200, 500, 1000 and 1500 mg/Kg i.p. caused cell damage and changes in F-actin distribution in the proximal tubule of male Wistar rats. After 48 hours of treatment, the proximal tubule epithelium showed tumefaction and necrosis. Dose of 200 mg/kg decreased the F-actin and was observed a structure in patches in the basal cytoplasm of epithelial cells of the proximal tubule. This effect was increased depending on the administered dose. Dose of 1000 mg/kg produced the highest histological damage and changes in the actin cytoskeleton. Results of this study suggested that nephrotoxic damage produced by high doses of APAP included breakdown of cytoskeleton in proximal tubule epithelium.
基金Supported by National Institutes of Health,No.DP2 OD008470Private funding was provided from the University of Notre Dame College of Science and Graduate Schoola generous donation to support stem cell research provided by the Gallagher Family
文摘Kidney disease is an escalating global health problem,for which the formulation of therapeutic approaches using stem cells has received increasing research attention.The complexity of kidney anatomy and function,which includes the diversity of renal cell types,poses formidable challenges in the identification of methods to generate replacement structures.Recent work using the zebrafish has revealed their high capacity to regenerate the integral working units of the kidney,known as nephrons,following acute injury.Here,we discuss these findings and explore the ways that zebrafish can be further utilized to gain a deeper molecular appreciation of renal stem cell biology,which may uncover important clues for regenerative medicine.
文摘Acute tubular necrosis(ATN)induced by ischemia is the most common insult to donor kidneysdestined for trarsplantation.ATN results from sweling and subsequent damage to cells lining thelkidney tubules.In this study,we demonstrate the capability of optical coherence tomography(OcT)to image the renal microst ructures of living human donor kidneys and potentially providea measure to det ermine the extent of A TN.We also found that Doppler-based OCT(i.e.,DOCT)reveals renal blood flow dynamics that is another major factor which could relate to post-transplant renal finction.All OCT/DoCT oberva tions were performed in a noninvasive,sterileand timely manner on intact human kidneys both prior to(er vivo)and following(in vivo)theirtransplantation.Our results indicate that this imaging model provides transplant surgeons withan objective visualization of the transplant lidneys prior and immediately post transplantation.
文摘Current dialysis systems are not perfect considering the low efficacy and cumbersome process of actual practice. To overcome these shortcomings, bioartificial kidneys using renal tubule cells and wearable dialysis are promising ESRD treatments available in the near future. Toward clinical application, however, there are so many obstacles for commercial use of them. In this review, current status of bioartificial kidneys such as the renal tubule cell assist device (RAD) and wearable dialysis devices is presented with the comparison to show the advantages and disadvantages.
文摘950350 Improving lithium clearance——a methodfor measuring sodium delivery of tubule in human.WANG Huamin(王化民),et al.Nephrol Div,1stTeach Hosp,Beijing Med Univ.Chin J Nephrol 1994;10(6):326-328.Based on the method for lithium clearance,we ob-served the relationship between serum lithium concen-tration at the fouth hour in the test and the representa-tive serum lithium concentration,and verified that
基金supported by the National Natural Science Foundation of China (81571396 and 81771528)Science, Technology and Innovation Commission of Shenzhen Municipality (JCYJ20170411090932146, JCYJ20170818110544730)。
文摘The mechanism of how SARS-CoV-2 causes severe multi-organ failure is largely unknown. Acute kidney injury(AKI) is one of the frequent organ damage in severe COVID-19 patients. Previous studies have shown that human renal tubule cells could be the potential host cells targeted by SARS-CoV-2. Traditional cancer cell lines or immortalized cell lines are genetically and phenotypically different from host cells. Animal models are widely used, but often fail to reflect a physiological and pathogenic status because of species tropisms. There is an unmet need for normal human epithelial cells for disease modeling. In this study, we successfully established long term cultures of normal human kidney proximal tubule epithelial cells(KPTECs) in 2 D and 3 D culture systems using conditional reprogramming(CR) and organoids techniques.These cells had the ability to differentiate and repair DNA damage, and showed no transforming property. Importantly, the CR KPTECs maintained lineage function with expression of specific transporters(SLC34 A3 and cubilin). They also expressed angiotensin-converting enzyme 2(ACE2), a receptor for SARS-CoV and SARS-CoV-2. In contrast, cancer cell line did not express endogenous SLC34 A3, cubilin and ACE2. Very interestingly, ACE2 expression was around twofold higher in 3 D organoids culture compared to that in 2 D CR culture condition. Pseudovirion assays demonstrated that SARS-CoV spike(S) protein was able to enter CR cells with luciferase reporter. This integrated 2 D CR and 3 D organoid cultures provide a physiological ex vivo model to study kidney functions, innate immune response of kidney cells to viruses, and a novel platform for drug discovery and safety evaluation.
