scholarly journals Regulation of Endothelial-to-Mesenchymal Transition by MicroRNAs in Chronic Allograft Dysfunction

2019 ◽  
Vol 103 (4) ◽  
pp. e64-e73 ◽  
Author(s):  
Emily K. Glover ◽  
Nina Jordan ◽  
Neil S. Sheerin ◽  
Simi Ali
Keyword(s):  
Chronic Allograft Dysfunction ◽  
Mesenchymal Transition ◽  
Allograft Dysfunction ◽  
Endothelial To Mesenchymal Transition

scholarly journals Cyclophilin A/CD147 Induces the Epithelial-to-mesenchymal Transition and Renal Fibrosis in Chronic Allograft Dysfunction by Regulating MAPK Signaling

2021 ◽  
Author(s):  
Xuzhong Liu ◽  
Zhiwang Tang ◽  
Xi Jiang ◽  
Tianwei Wang ◽  
Lun Zhao ◽  
...  
Keyword(s):  
Renal Transplant ◽  
Epithelial To Mesenchymal Transition ◽  
Renal Allograft ◽  
Cyclophilin A ◽  
Mapk Signaling ◽  
Chronic Allograft Dysfunction ◽  
Mesenchymal Transition ◽  
Allograft Dysfunction

Abstract Objectives: Our study was designed to explore the role of Cyclophilin A (CyPA)/CD147 interactions in renal allograft fibrosis and chronic allograft dysfunction (CAD). Methods and materials: A rat renal transplant model with significant CAD was successfully identified. Renal allograft tissues and blood samples were collected. HE, Masson and immunohistochemistry staining were performed. Then human HK-2 cells were intervened by certain concentrations of CyPA, and total protein and mRNA were extracted. Western blot assay and PCR were performed to explore the protein and mRNA expression of CyPA, CD147 and epithelial-to-mesenchymal transition (EMT)-related biomarkers. CD147 siRNA and specific inhibitor of MAPK were used to explore the involved cellular mechanism.Results: We have successfully established and identified a 20-weeks renal transplant CAD model. We observed significant distributed and expressed CyPA and CD147 in the renal allograft fibrosis tissues. We also found the significant expression of CD147 and EMT-related markers in the HK-2 cells stimulated by CyPA. The CD147 siRNA confirmed the previous results in vitro. The selective inhibition of MAPK suggested the notable role of MAPK signaling pathway in the CyP/CD147 interactions involved in renal allograft fibrosis.Conclusions: Our study reported the positive relationship of CyPA/CD147 interactions with the renal allograft dysfunction. In vitro study suggested that CyPA could bind to CD147 and then induce the development of EMT process by MAPK signaling, thus contributing to the renal allograft fibrosis and CAD.

scholarly journals Biological Effects of XyloCore, a Glucose Sparing PD Solution, on Mesothelial Cells: Focus on Mesothelial-Mesenchymal Transition, Inflammation and Angiogenesis

Nutrients ◽  
2021 ◽  
Vol 13 (7) ◽  
pp. 2282
Author(s):  
Valentina Masola ◽  
Mario Bonomini ◽  
Maurizio Onisto ◽  
Pietro Manuel Ferraro ◽  
Arduino Arduini ◽  
...  
Keyword(s):  
Endothelial Cell ◽  
Cell Viability ◽  
Biological Effects ◽  
Membrane Integrity ◽  
Glucose Content ◽  
Mesenchymal Transition ◽  
Low Glucose ◽  
Endothelial To Mesenchymal Transition ◽  
Osmotic Agents

Glucose-based solutions remain the most used osmotic agents in peritoneal dialysis (PD), but unavoidably they contribute to the loss of peritoneal filtration capacity. Here, we evaluated at a molecular level the effects of XyloCore, a new PD solution with a low glucose content, in mesothelial and endothelial cells. Cell viability, integrity of mesothelial and endothelial cell membrane, activation of mesothelial and endothelial to mesenchymal transition programs, inflammation, and angiogenesis were evaluated by several techniques. Results showed that XyloCore preserves mesothelial and endothelial cell viability and membrane integrity. Moreover XyloCore, unlike glucose-based solutions, does not exert pro-fibrotic, -inflammatory, and -angiogenic effects. Overall, the in vitro evidence suggests that XyloCore could represent a potential biocompatible solution promising better outcomes in clinical practice.

scholarly journals Burn-induced heterotopic ossification from incidence to therapy: key signaling pathways underlying ectopic bone formation

2021 ◽  
Vol 26 (1) ◽  
Author(s):  
Xianglin Hu ◽  
Zhengwang Sun ◽  
Fengfeng Li ◽  
Chaoyin Jiang ◽  
Wangjun Yan ◽  
...  
Keyword(s):  
Growth Factor ◽  
Heterotopic Ossification ◽  
Transforming Growth Factor ◽  
Burn Injury ◽  
Hypoxia Inducible Factor ◽  
Total Body Surface Area ◽  
Adaptive Immune System ◽  
Transforming Growth Factor Β1 ◽  
Mesenchymal Transition ◽  
Endothelial To Mesenchymal Transition

AbstractBurn injury is one of the potential causes of heterotopic ossification (HO), which is a rare but debilitating condition. The incidence ranges from 3.5 to 5.6 depending on body area. Burns that cover a larger percentage of the total body surface area (TBSA), require skin graft surgeries, or necessitate pulmonary intensive care are well-researched risk factors for HO. Since burns initiate such complex pathophysiological processes with a variety of molecular signal changes, it is essential to focus on HO in the specific context of burn injury to define best practices for its treatment. There are numerous key players in the pathways of burn-induced HO, including neutrophils, monocytes, transforming growth factor-β1-expressing macrophages and the adaptive immune system. The increased inflammation associated with burn injuries is also associated with pathway activation. Neurological and calcium-related contributions are also known. Endothelial-to-mesenchymal transition (EMT) and vascularization are known to play key roles in burn-induced HO, with hypoxia-inducible factor-1 (HIF-1) and vascular endothelial growth factor (VEGF) as potential initiators. Currently, non-steroidal anti-inflammatory drugs (NSAIDs) and radiotherapy are effective prophylaxes for HO. Limited joint motion, ankylosis and intolerable pain caused by burn-induced HO can be effectively tackled via surgery. Effective biomarkers for monitoring burn-induced HO occurrence and bio-prophylactic and bio-therapeutic strategies should be actively developed in the future.

scholarly journals Endothelial-to-mesenchymal transition in lipopolysaccharide-induced acute lung injury drives a progenitor cell-like phenotype

2016 ◽  
Vol 310 (11) ◽  
pp. L1185-L1198 ◽  
Author(s):  
Toshio Suzuki ◽  
Yuji Tada ◽  
Rintaro Nishimura ◽  
Takeshi Kawasaki ◽  
Ayumi Sekine ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Endothelial Cells ◽  
Acute Lung Injury ◽  
Lung Injury ◽  
Vascular Endothelial Cells ◽  
Repair Process ◽  
Vascular Endothelial ◽  
Mesenchymal Transition ◽  
Oxidase Inhibition ◽  
Endothelial To Mesenchymal Transition

Pulmonary vascular endothelial function may be impaired by oxidative stress in endotoxemia-derived acute lung injury. Growing evidence suggests that endothelial-to-mesenchymal transition (EndMT) could play a pivotal role in various respiratory diseases; however, it remains unclear whether EndMT participates in the injury/repair process of septic acute lung injury. Here, we analyzed lipopolysaccharide (LPS)-treated mice whose total number of pulmonary vascular endothelial cells (PVECs) transiently decreased after production of reactive oxygen species (ROS), while the population of EndMT-PVECs significantly increased. NAD(P)H oxidase inhibition suppressed EndMT of PVECs. Most EndMT-PVECs derived from tissue-resident cells, not from bone marrow, as assessed by mice with chimeric bone marrow. Bromodeoxyuridine-incorporation assays revealed higher proliferation of capillary EndMT-PVECs. In addition, EndMT-PVECs strongly expressed c- kit and CD133. LPS loading to human lung microvascular endothelial cells (HMVEC-Ls) induced reversible EndMT, as evidenced by phenotypic recovery observed after removal of LPS. LPS-induced EndMT-HMVEC-Ls had increased vasculogenic ability, aldehyde dehydrogenase activity, and expression of drug resistance genes, which are also fundamental properties of progenitor cells. Taken together, our results demonstrate that LPS induces EndMT of tissue-resident PVECs during the early phase of acute lung injury, partly mediated by ROS, contributing to increased proliferation of PVECs.

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