Alleviation of ischemia-reperfusion induced renal injury by chemically modified SOD2 mRNA delivered via lipid nanoparticles.

Ischemia-reperfusion injury (IRI) is a major cause of acute kidney injury, which is a serious clinical condition with no effective pharmacological treatment. Mesenchymal stem cell-derived extracellular vesicles (MSC-EVs) significantly alleviate kidney IRI; however, the underlying mechanisms and key molecules conferring renoprotection remain elusive. In this study, we characterized the protein composition of MSC-EVs using a proteomics approach and found that mitochondrial protein superoxide dismutase 2 (SOD2) was enriched in MSC-EVs. Using lipid nanoparticles (LNP), we successfully delivered chemically modified SOD2 mRNA into kidney cells and mice with kidney IRI. We demonstrated that SOD2 mRNA-LNP treatment decreased cellular reactive oxygen species (ROS) in cultured cells and ameliorated renal damage in IRI mice, as indicated by reduced levels of serum creatinine and restored tissue integrity compared with the control mRNA-LNP-injected group. Thus, the modulation of mitochondrial ROS levels through SOD2 upregulation by SOD2 mRNA-LNP delivery could be a novel therapeutic method for ischemia-reperfusion-induced acute kidney injury.

Cofilin-1 induces acute kidney injury via the promotion of endoplasmic reticulum stress-mediated ferroptosis.

Ischemia-reperfusion injury (IRI) leads to acute kidney injury (AKI), which poses serious threat to public health and society. Many clinical studies were conducted to evaluate several biomarkers in AKI, among which Cofilin-1 remains to be a very promising one. To explore the potential mechanism of Cofilin-1 in AKI, we established an oxygen-glucose-deprivation (OGD)-induced AKI cell model. The overexpression and knock-down Cofilin-1 were used for gain- and loss-of-function. Pharmacological inhibitors were employed to study the related pathways. The results showed that Cofilin-1 was significantly upregulated in AKI cells, knocking down Cofilin-1 protected cells against the effect of OGD treatment and alleviated AKI phenotypes. Overexpression of Cofilin-1 might induce AKI by triggering ferroptosis, inhibiting NF-κB signaling or ER stress pathway attenuated Cofilin-1 induced lipid peroxidation and AKI. We also validated our findings in IRI-induced AKI mouse models in vivo. Our work elucidated that Cofilin-1 might induce AKI via promoting ER stress-mediated ferroptosis and argues it as a biomarker for early diagnosis of AKI. We also expect to offer novel insights on future therapeutic interventions.

A Bibliometric Analysis of Urologic Chronic Pelvic Pain Syndrome From 2000 to 2022.

Purpose: Urologic chronic pelvic pain syndrome has attracted a lot of attention in the new century, and an increasing number of relevant studies have been published. Therefore, we performed a bibliometric analysis of these publications, hoping to show the current research hotspots and future research trends. Methods: The articles on were selected from the Web of Science Core Collection. Countries, authors, references and keywords in the field were visualized and analyzed using CiteSpace and VOSViewer software. Results: A total of 1014 articles on urologic chronic pelvic pain syndrome were identified, with "chronic pelvic pain syndrome" being the most common keyword, with a strong association with "interstitial cystitis" and "chronic prostatitis". The hotspot of urologic chronic pelvic pain syndrome research has gradually shifted from chronic prostatitis / urologic chronic pelvic pain syndrome to cystitis/bladder pain syndrome over the past few years. Future research tends to focus on urologic chronic pelvic pain syndrome etiology, including oxidative stress and inflammation. Conclusion: Research on urologic chronic pelvic pain syndrome is steadily growing. The United States has made the most prominent contribution in this area, and the share of China's contribution is expected to grow further. The etiology of urologic chronic pelvic pain syndrome, including inflammation and oxidative stress, have been the focus of current research and developmental trends in the future research.

Renal denervation alleviates renal ischemic reperfusion injury-induced acute and chronic kidney injury in rats partly by modulating miRNAs.

BACKGROUND: Renal denervation (RDN) has been used to promote kidney injury repair, whereas miRNAs have been found to be involved in the pathophysiology of renal injury. However, the miRNA alterations that occur after RDN and the related protective mechanisms remain to be determined. METHODS: Renal ischemic reperfusion injury (IRI) rat model was established and RDN was performed. Animals were killed at 24 h and 2 weeks following the operation. Tyrosine hydroxylase (TH) levels, renal function, tubular cell apoptosis and histological sections were examined at 24 h, whereas renal fibrosis and capillary vessels were assessed at 2 weeks. Furthermore, the expression of miRNAs in the injured kidney was determined using micro-array and the target genes were analyzed. RESULTS: We found that TH was eliminated and that renal function was improved in the denervation group at 24 h. RDN reduced tubular cell apoptosis and mitigated the histological lesion. Furthermore, an increase of capillary vessel density and reduction of renal fibrosis were observed after 2 weeks. Moreover, the numbers of miRNAs were up-regulated after RDN treatment, and the miRNAs targeted pro-angiogenic, anti-fibrotic and inflammatory pathways. CONCLUSIONS: RDN is a reliable method for alleviating IRI-induced acute and chronic kidney injury, and modulating the miRNA-related pro-angiogenic, anti-fibrotic or inflammatory pathways involved in this process.

Non-apoptotic function of caspase-8 confers prostate cancer enzalutamide resistance via NF-κB activation.

Caspase-8 is a unique member of caspases with a dual role in cell death and survival. Caspase-8 expression is often lost in some tumors, but increased in others, indicating a potential pro-survival function in cancer. By analyzing transcriptome of enzalutamide-resistant prostate cancer cells, we found that resistance was conferred by a mild caspase-8 upregulation that in turn led to NF-κB activation and the subsequent upregulation of the downstream IL-8. Mechanistically, we found that the pro-survival and enzalutamide-resistance-promoting features of caspase-8 were independent of its proteolytic activity, using a catalytically-inactive caspase-8 mutant. We further demonstrated that caspase-8 pro-apoptotic function was inhibited via cFLIP binding. Moreover, high caspase-8 expression was correlated with a worse prognosis in prostate cancer patients. Collectively, our work demonstrates that enzalutamide-resistance is mediated by caspase-8 upregulation and the consequent increase in NF-κB/IL-8 mediated survival signaling, highlighting caspase-8 and NF-κB as potential therapeutic targets to overcome enzalutamide-resistance in CRPC.

MiR-197 Inhibitor Loaded AbCD133@MSNs@GNR Affects the Development of Prostate Cancer Through Targeting ITGAV.

Prostate cancer is one of the most severe male malignant tumors, which ranks second in mortality rate among all tumors. Traditional methods of treatment for prostate cancer produce obvious side effects and a high recurrence rate. Cancer stem cells are considered to be a group of cells that determine the proliferation, metastasis, and drug resistance of tumor. Prostate cancer therapy based on microRNAs and prostate cancer stem cells (PCSCs) has been a research hot spot in this field. Previous studies have reported that miR-197 plays an important role in the occurrence and development of prostate cancer, but the molecular mechanism of miR-197 on the development of prostate cancer has not been reported yet. In this study, we verified that miR-197 is significantly overexpressed in prostate cancer tissues and prostate cancer cells. Then, we verified that miR-197 expression affects the proliferation, invasion, and metastasis of prostate cancer cells by regulating integrin subunit alpha V (ITGAV) expression through STAT5 pathway, and the results indicated that the miR-197 inhibitor can be a prostate cancer suppressor. Then we synthesized the AbCD133@GNR@MSNs@miR-197 inhibitor drug carrier, in which 35.42 µg of the miR-197 inhibitor could be loaded in 1 mg of AbCD133@GNR@MSNs. The AbCD133@GNR@MSNs@miR-197 inhibitor demonstrated good photothermal properties and photothermal controlled-release properties. The modified CD133 antibodies on the surface of the nano drug carrier helped more drug carriers to enter the PCSCs. The pharmacodynamic effects of the AbCD133@GNR@MSNs@miR-197 inhibitor on PCSCs in vivo and in vitro were studied under near-infrared radiation. The results showed that the AbCD133@GNR@MSNs@miR-197 inhibitor prepared in this study could not only significantly suppress the development of PCSCs through ITGAV/STAT5 pathway but also significantly suppress the growth of PCSC solid tumors. In short, our study verified that miR-197 regulates the development of PCSCs through STAT5 pathway by targeting ITGAV, and the AbCD133@MSNs@GNR@miR-197 inhibitor could be a potential suppressor used in prostate cancer treatment. In short, our study found that miR-197 affected the development of prostate cancer by regulating ITGAV. The AbCD133@GNR@MSNs@miR-197 inhibitor prepared in this study could suppress the development and growth of PCSCs in vitro and in solid tumors not only by targeting the ITGAV but also through photothermal therapy. Our study not only provides a theoretical basis for the clinical treatment of prostate cancer but also provides a research scheme of drug loading and microRNA-based photothermal controlled therapy for prostate cancer.

Comprehensive miRNA Analysis of Human Umbilical Cord-Derived Mesenchymal Stromal Cells and Extracellular Vesicles.

BACKGROUND/AIMS: Mesenchymal stromal cells (MSCs) participate in the tissue-specific repair of many different organs, especially the kidney. Their effects are primarily mediated by the paracrine release of factors including extracellular vesicles (EVs), which are composed of micro-vesicles and exosomes. The corresponding microRNAs (miRNAs) of EVs are considered important for their biological functions. METHODS: MSCs were cultured from the human umbilical cord, and EVs were isolated from the medium. The expression levels of miRNAs in MSCs and EVs were determined by microarray analysis, and gene ontology (GO) was used to analyze the functions of their target genes. RESULTS: MSCs and EVs had similar miRNA expression profiles, with the exception of a small number of selectively enriched miRNAs. GO analysis indicated that, unlike MSCs, the target genes of EV-enriched miRNAs were associated with calcium channel regulation and cell junction activities, which may indicate that MSC and EVs have different regulatory properties. Angiogenesis, oxidative stress, and inflammatory signaling pathways related to the repair of renal injury were also analyzed, and EV-enriched miRNAs targeted genes associated with oxidative stress, T cell activation, and Toll-like receptor signaling. The miRNAs enriched in both MSCs and EVs targeted different genes in signaling pathways regulating angiogenesis and chemokine release. CONCLUSION: MSCs and their EVs shared similar miRNA component, and some selectively enriched miRNAs observed in MSCs and EVs may affect different target genes through some specific signaling pathways.

Hypoxia-induced extracellular vesicles mediate protection of remote ischemic preconditioning for renal ischemia-reperfusion injury.

Remote ischemic preconditioning (rIPC) is a reliable strategy for prevention of injury to various organs. However the mechanism by which it does so is still unclear. In the present study, serum and EVs isolated from ischemic preconditioned right renal venous perfusates were injected into rats with ischemia-reperfusion-injured kidneys immediately after reperfusion. The animals were killed 24h later. Tubular scores and renal function were tested to evaluate the therapeutic effects. To further explore the underlying mechanism, HK-2 cells derived EVs under hypoxia were also administrated to rats with left kidney IRI. Results showed that transient ischemia of the right kidney induced renal tubular epithelial cells to release functional extracellular vesicles (EVs), which were found to alleviate left kidney ischemic reperfusion injury (IRI) by circulation and the EV-depleted serum lost this property. Further, human kidney cells (HK2) were cultured under hypoxic conditions to generate EVs in vitro. These EVs also showed obvious therapeutic effects for renal IRI. Our results suggested that remote ischemic preconditioning plays a therapeutic role in renal IRI through EVs induced by hypoxia.

Human mesenchymal stromal cell-derived extracellular vesicles alleviate renal ischemic reperfusion injury and enhance angiogenesis in rats.

BACKGROUND: Mesenchymal stromal cells (MSCs) derived extracellular vesicles (EVs) were regarded as a potent medium for kidney injury repair and angiogenesis were regarded as an important step in tissue regeneration. However, the pro-angiogenesis effect of MSC-EVs in ischemia-reperfusion induced kidney injury and its potential mechanisms have yet to be determined. METHODS: EVs were isolated from the medium of human umbilical cord-derived MSCs (huMSCs) were injected in rats intravenously after unilateral kidney ischemia. Animals were sacrificed at 24 h and 2 weeks after injury. The renal functions and histology staining were examined to assess the therapeutic effect of the EVs. Moreover, we investigated the pro-angiogenesis effects of EVs in injured kidneys and tested the angiogenesis-related factors to further illuminate the probable mechanisms. RESULTS: It was observed that EVs could reduce cell apoptosis and enhances proliferation 24 h after kidney injury, meanwhile renal function was improved and the histological lesion was mitigated. Moreover, renal VEGF was up-regulated by EVs and HIF-1α was down-regulated. Further, the increase of capillary vessel density and reduce of renal fibrosis was observed after 2 weeks. In vitro, EVs could deliver human VEGF directly to renal tubular epithelial cells (TECs) and increase VEGF levels. Most important, all the beneficial effects of EVs were abrogated by RNase treated except for the delivery of human VEGF. CONCLUSIONS: Human MSC-EVs could protect against ischemic/reperfusion injury induced kidney injury through pro-angiogenesis effects in HIF-1α independent manner, and both the delivery of pro-angiogenesis related VEGF and RNAs were involved in this process.

Mesenchymal Stromal Cells Derived Extracellular Vesicles Ameliorate Acute Renal Ischemia Reperfusion Injury by Inhibition of Mitochondrial Fission through miR-30.

Background. The immoderation of mitochondrial fission is one of the main contributors in ischemia reperfusion injury (IRI) and mesenchymal stromal cells (MSCs) derived extracellular vesicles have been regarded as a potential therapy method. Here, we hypothesized that extracellular vesicles (EVs) derived from human Wharton Jelly mesenchymal stromal cells (hWJMSCs) ameliorate acute renal IRI by inhibiting mitochondrial fission through miR-30b/c/d. Methods. EVs isolated from the condition medium of MCS were injected intravenously in rats immediately after monolateral nephrectomy and renal pedicle occlusion for 45 minutes. Animals were sacrificed at 24 h after reperfusion and samples were collected. MitoTracker Red staining was used to see the morphology of the mitochondria. The expression of DRP1 was measured by western blot. miR-30 in EVs and rat tubular epithelial cells was assessed by qRT-PCR. Apoptosis pathway was identified by immunostaining. Results. We found that the expression of miR-30 in injured kidney tissues was declined and mitochondrial dynamics turned to fission. But they were both restored in EVs group in parallel with reduced cell apoptosis. What is more, when the miR-30 antagomirs were used to reduce the miRNA levels, all the related effects of EVs reduced remarkably. Conclusion. A single administration of hWJMSC-EVs could protect the kidney from IRI by inhibition of mitochondrial fission via miR-30.

microRNA-372 Suppresses Migration and Invasion by Targeting p65 in Human Prostate Cancer Cells.

Prostate cancer (PCa) is one of the most prevalent malignant tumors. microRNAs (miRNAs) play an important role in cancer initiation, progression, and metastasis, and their roles in PCa are becoming more apparent. In this study, we found that microRNA-372 (miR-372) is downregulated in human PCa and inhibits the proliferation activity, migration, and invasion of DU145 cells. Subsequently, p65 is confirmed as a target of miR-372, and knockdown of p65 expression similarly resulted in decreased proliferation activity, migration, and invasion. CDK8, MMP-9, and prostate-specific antigen were involved in both these processes. Taken together, our results show evidence that miR-372 may function as a tumor suppressor gene by regulating p65 in PCa and may provide a strategy for blocking PCa metastasis.

NK Cell Regulatory Property is Involved in the Protective Role of MSC-Derived Extracellular Vesicles in Renal Ischemic Reperfusion Injury.

Immunomodulation has been regarded as an important therapeutic aspect of mesenchymal stromal cell-derived extracellular vesicles (MSC-EVs) in renal ischemic reperfusion injury (IRI), and the specific mechanism still unclear. Here, we attempt to test the function of human MSC-EVs on renal IRI by targeting the natural killer (NK) cells and to investigate the possible mechanism. Data indicated that EVs decreased NK cells in spleen and ischemic kidney. Both the EVs and antibody-dependent depletion of NK cells displayed a protective role in IRI rats. Moreover, the splenectomy model was established to evaluate the role of spleen in this process. It showed that the NK cell regulatory ability and renal protective effects by EVs still exist without spleen, which is unlike MSC properties published previously. Further, the down-regulation of chemokines in injured kidney and the delivery of RNAs through EVs in vitro were also observed. Through the microRNA array test, various inflammation-related microRNAs highly expressed in MSC-EVs compared with fibroblast EVs were tested. Thus, these results indicated that MSC-EVs could ameliorate renal ischemic reperfusion injury by decreasing NK cells and the spleen is not necessary in this process. The regulation of chemokines in injured kidney was the other factor, and the transfer of various microRNAs in the MSC-EVs may be involved. This provides direction for future clinical applications.

Extracellular vesicles derived from mesenchymal stromal cells may possess increased therapeutic potential for acute kidney injury compared with conditioned medium in rodent models: A meta-analysis.

The potential involvement of the endocrine/paracrine mechanisms in the mesenchymal stromal cells (MSCs) therapy for acute kidney injury (AKI) has been increasingly studied. The aim of the present meta-analysis was to systematically review the therapeutic role of MSC-conditioned medium (CM) or MSCs released by extracellular vesicles (Evs) for the treatment of AKI in rodent models. Studies were identified using PubMed and Scopus databases using a custom search strategy and eligibility criteria. Data regarding serum creatinine (SCr) concentration, CM or Evs, measurement time point, AKI model (toxic or non-toxic) and other parameters, including delivery route, animal type and animal numbers, were extracted. Pooled analysis and subgroup analysis as well as multivariable meta-regression were performed. Heterogeneity and publication bias were also investigated. A total of 13 studies were included and analyzed. Pooled analysis showed reduced SCr (0.93 [0.67, 1.20], mg/dl) in rodent models of AKI after CM/Evs therapy. The results of the subgroup analysis suggested that Evs induced an increased therapeutic effect, in the form of SCr reduction, as compared with CM (P=0.05). There were also other significant influential factors for SCr reduction including measurement time point (P=0.0004) and therapeutic time point (P<0.0001) after surgery. By contrast, parameters such as delivery route, injury type and cell type were not significant influential factors. Multivariable meta-regression analysis showed that measurement time point (P=0.041), therapeutic time point (P=0.03), Evs or CM (P=0.0003) and cell type (P<0.0001) were influential factors in the reduction of SCr. The present meta-analysis indicates that CM or Evs derived from MSCs are able to improve the impaired renal function in rodents modelling AKI. Compared with CM, Evs may produce a more marked therapeutic effect in recovery from renal failure. In addition, CM or Evs administration in early stages of AKI may result in more evident effects.

Mesenchymal Stromal Cell-Derived Extracellular Vesicles Protect Against Acute Kidney Injury Through Anti-Oxidation by Enhancing Nrf2/ARE Activation in Rats.

BACKGROUND/AIMS: Anti-oxidation is an effective strategy for curing acute kidney injury (AKI). Herein, we suggest that extracellular vesicles (EVs) derived from mesenchymal stromal cells (MSCs) might play an anti-oxidative role by enhancing Nrf2/ARE activation in AKI. METHODS: EVs isolated from the conditioned medium of human Wharton's Jelly mesenchymal stromal cells and human foreskin fibroblast were intravenously injected in rats immediately after 45 min of unilateral kidney ischemia. Animals were sacrificed 24 h after injury. RESULTS: Results showed that renal tubular injury was alleviated and renal function was improved by MSC-EVs. Cell apoptosis and sNGAL levels, which reflect kidney cell injury, were reduced. Moreover, MSC-EVs decreased oxidative stress in injured kidney tissues and NRK-52E cells under hypoxia injury. Nrf2/antioxidant response element (ARE) enhancement and HO-1 up-regulation were further observed after MSC-EV treatment both in vivo and in vitro. CONCLUSIONS: MSC-EVs may protect against AKI possibly through anti-oxidation by enhancing Nrf2/ARE activation.

Differentiation of human umbilical cord mesenchymal stem cells into steroidogenic cells in vitro.

Although previous studies have shown that stem cells can be differentiated into Leydig cells by gene transfection, a simple, safe and effective induction method has not yet been reported. Therefore, the present study investigated novel methods for the induction of human umbilical cord mesenchymal stem cell (HUMSC) differentiation into Leydig-like, steroidogenic cells. HUMSCs were acquired using the tissue block culture attachment method, and the expression of MSC surface markers was evaluated by flow cytometry. Leydig cells were obtained by enzymatic digestion and identified by lineage-specific markers via immunofluorescence. Third-passage HUMSCs were cultured with differentiation-inducing medium (DIM) or Leydig cell-conditioned medium (LC-CM), and HUMSCs before induction were used as the control group. Following the induction of HUMSCs, Leydig cell lineage-specific markers (CYP11A1, CYP17A1 and 3ß-HSD) were positively identified using immunofluorescence analysis. Additionally, reverse transcription-quantitative polymerase chain reaction and western blot analysis were performed to evaluate the expression levels of these genes and enzymes. In contrast, the control group cells did not show the characteristics of Leydig cells. Collectively, these results indicate that, under in vitro conditions, LC-CM can achieve a comparable effect to that of DIM on inducing HUMSCs differentiation into steroidogenic cells.

Tumor-suppressive microRNA-497 targets IKKß to regulate NF-κB signaling pathway in human prostate cancer cells.

BACKGROUND: Prostate cancer (PCa) is one of the most prevalent malignant tumors, PCa-related death is mainly due to the high probability of metastasis. MicroRNAs (miRNAs) play an important role in cancer initiation, progression and metastasis by regulating their target genes. METHODS: real-time PCR was used to detected the expression of microRNA-497. The molecular biological function was investigated by using cell proliferation assays, cell cycle assay, and migration and invasion assay. We used several Algorithms and confirmed that IKKß is directly regulated by miR-497. RESULTS: Here, we found miR-497 is downregulated in human prostate cancer (PCa) and inhibites the proliferation activity, migration and invasion of PC3-AR cells. Subsequently, IKKß is confi rmed as a target of miR-497. Furthermore, knockdown of IKKß expression resulted in decreased proliferation activity, migration and invasion. Finally, similar results was found after treatment with a novel IKK-ß inhibitor (IMD-0354) in PC3-AR cells. CDK8, MMP-9, and PSA were involved in all these process. CONCLUSION: Taken together, our results show evidence that miR-497 may function as a tumor suppressor genes by regulating IKK-ß in PCa, and may provide a strategy for blocking PCa metastasis.

Time-dependent bladder tissue regeneration using bilayer bladder acellular matrix graft-silk fibroin scaffolds in a rat bladder augmentation model.

With advances in tissue engineering, various synthetic and natural biomaterials have been widely used in tissue regeneration of the urinary bladder in rat models. However, reconstructive procedures remain insufficient due to the lack of appropriate scaffolding, which should provide a waterproof barrier function and support the needs of various cell types. To address these problems, we have developed a bilayer scaffold comprising a porous network (silk fibroin [SF]) and an underlying natural acellular matrix (bladder acellular matrix graft [BAMG]) and evaluated its feasibility and potential for bladder regeneration in a rat bladder augmentation model. Histological (hematoxylin and eosin and Masson's trichrome staining) and immunohistochemical analyses demonstrated that the bilayer BAMG-SF scaffold promoted smooth muscle, blood vessel, and nerve regeneration in a time-dependent manner. At 12weeks after implantation, bladders reconstructed with the BAMG-SF matrix displayed superior structural and functional properties without significant local tissue responses or systemic toxicity. These results demonstrated that the bilayer BAMG-SF scaffold may be a promising scaffold with good biocompatibility for bladder regeneration in the rat bladder augmentation model.

Microvesicles derived from human umbilical cord mesenchymal stem cells facilitate tubular epithelial cell dedifferentiation and growth via hepatocyte growth factor induction.

During acute kidney injury (AKI), tubular cell dedifferentiation initiates cell regeneration; hepatocyte growth factor (HGF) is involved in modulating cell dedifferentiation. Mesenchymal stem cell (MSC)-derived microvesicles (MVs) deliver RNA into injured tubular cells and alter their gene expression, thus regenerating these cells. We boldly speculated that MVs might induce HGF synthesis via RNA transfer, thereby facilitating tubular cell dedifferentiation and regeneration. In a rat model of unilateral AKI, the administration of MVs promoted kidney recovery. One of the mechanisms of action is the acceleration of tubular cell dedifferentiation and growth. Both in vivo and in vitro, rat HGF expression in damaged rat tubular cells was greatly enhanced by MV treatment. In addition, human HGF mRNA present in MVs was delivered into rat tubular cells and translated into the HGF protein as another mechanism of HGF induction. RNase treatment abrogated all MV effects. In the in vitro experimental setting, the conditioned medium of MV-treated injured tubular cells, which contains a higher concentration of HGF, strongly stimulated cell dedifferentiation and growth, as well as Erk1/2 signaling activation. Intriguingly, these effects were completely abrogated by either c-Met inhibitor or MEK inhibitor, suggesting that HGF induction is a crucial contributor to the acceleration of cell dedifferentiation and growth. All these findings indicate that MV-induced HGF synthesis in damaged tubular cells via RNA transfer facilitates cell dedifferentiation and growth, which are important regenerative mechanisms.

The regulation of inflammatory mediators in acute kidney injury via exogenous mesenchymal stem cells.

Acute kidney injury (AKI) remains to be an independent risk factor for mortality and morbidity. Inflammation is believed to play a major role in the pathophysiology of AKI. Exogenous mesenchymal stem cells (MSCs) are now under extensive investigation as a potential therapy for AKI. Various preclinical studies indicated the beneficial effects of MSCs in alleviating renal injury and accelerating tissue repair. However the mechanisms responsible for these effects are incompletely understood. In the recent years, anti-inflammatory/immunoregulatory properties of MSCs have become one of the important issues in the treatment of AKI. This review will summarize the current literature on the regulation of inflammatory mediators via exogenous MSCs contributing to the recovery from AKI.