LPS-Binding Protein Modulates Acute Renal Fibrosis by Inducing Pericyte-to-Myofibroblast Trans-Differentiation through TLR-4 Signaling

Tanaka

et al. 2020

IJMS

Ischemic stroke caused by cerebral artery occlusion induces neurological deficits because of cell damage or death in the central nervous system. Given the recent therapeutic advances in reperfusion therapies, some patients can now recover from an ischemic stroke with no sequelae. Currently, reperfusion therapies focus on rescuing neural lineage cells that survive in spite of decreases in cerebral blood flow. However, vascular lineage cells are known to be more resistant to ischemia/hypoxia than neural lineage cells. This indicates that ischemic areas of the brain experience neural cell death but without vascular cell death. Emerging evidence suggests that if a vascular cell-mediated healing system is present within ischemic areas following reperfusion, the therapeutic time window can be extended for patients with stroke. In this review, we present our comments on this subject based upon recent findings from lethal ischemia following reperfusion in a mouse model of stroke.

Section: Findings After Early Reperfusion Under Lethal Ischemia Inmentioning

confidence: 99%

How Long Are Reperfusion Therapies Beneficial for Patients after Stroke Onset? Lessons from Lethal Ischemia Following Early Reperfusion in a Mouse Model of Stroke

Tanaka

et al. 2020

IJMS

“…Therefore, the development of novel therapies to improve renal regeneration capacity after AKI, to preserve renal function, and to prevent AKI is urgently needed. In this context, we wanted to offer a forum for the publication of new results on renal inflammation, injury and regeneration, as well as for the review and discussion of existing studies from this interesting research field.This Special Issue covers research articles that investigated the molecular mechanisms of inflammation [1-3] and injury [4,5] during different renal pathologies and renal regeneration [6], diagnostics using new biomarkers [7-9], and the effects of different stimuli like medication or bacterial components on isolated renal cells or in vivo models [10][11][12], all of which were summarized in a very simplified manner. Furthermore, this Special Issue contains important reviews that dealt with the current knowledge of cell death and regeneration [13,14], inflammation [15][16][17][18], and the molecular mechanisms of kidney diseases [19][20][21][22].…”

mentioning

confidence: 99%

“…This Special Issue covers research articles that investigated the molecular mechanisms of inflammation [1][2][3] and injury [4,5] during different renal pathologies and renal regeneration [6], diagnostics using new biomarkers [7][8][9], and the effects of different stimuli like medication or bacterial components on isolated renal cells or in vivo models [10][11][12], all of which were summarized in a very simplified manner. Furthermore, this Special Issue contains important reviews that dealt with the current knowledge of cell death and regeneration [13,14], inflammation [15][16][17][18], and the molecular mechanisms of kidney diseases [19][20][21][22].…”

mentioning

confidence: 99%

“…No injury or inflammatory effects of two anti-diabetically used gliflozins on proximal tubular epithelial cells that were cultured in hyperglycemic conditions were found [10]. Stimulations with bacterial lipopolysaccharide were used to investigate acute renal fibrosis in a model of sepsis-induced AKI [11] and the inflammatory cascade of obese kidney fibrosis in a metabolic endotoxemia mouse model [12].…”

mentioning

confidence: 99%

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Kidney Inflammation, Injury and Regeneration

Baer

Koch

Geiger

2020

IJMS

Damage to kidney cells can occur due to a variety of ischemic and toxic insults and leads to inflammation and cell death, which can result in acute kidney injury (AKI). Inflammation plays a key role in the injury of renal cells, as well as subsequent cellular regeneration processes. However, persistent chronic inflammation may trigger renal fibrosis. The investigation of the molecular mechanisms involved in each individual injury is currently insufficiently elucidated. Whereas the kidney has a remarkable capacity for regeneration after injury and may completely recover depending on the type of renal lesions, the options for clinical intervention are restricted to fluid management and extracorporeal kidney support. AKI is still associated with high morbidity and mortality incidence rates, and it also bears an elevated risk of subsequent chronic kidney disease. Therefore, the development of novel therapies to improve renal regeneration capacity after AKI, to preserve renal function, and to prevent AKI is urgently needed. In this context, we wanted to offer a forum for the publication of new results on renal inflammation, injury and regeneration, as well as for the review and discussion of existing studies from this interesting research field.This Special Issue covers research articles that investigated the molecular mechanisms of inflammation [1-3] and injury [4,5] during different renal pathologies and renal regeneration [6], diagnostics using new biomarkers [7-9], and the effects of different stimuli like medication or bacterial components on isolated renal cells or in vivo models [10][11][12], all of which were summarized in a very simplified manner. Furthermore, this Special Issue contains important reviews that dealt with the current knowledge of cell death and regeneration [13,14], inflammation [15][16][17][18], and the molecular mechanisms of kidney diseases [19][20][21][22]. In addition, the potential of cell-based therapy approaches that use mesenchymal stromal/stem cells (MSCs) or their derivates is summarized [23][24][25]. This edition is complemented by a series of reviews that deal with the current data situation on other very specific topics like diabetes and diabetic nephropathy [26][27][28], as well as new therapeutic targets [29].In this Special Issue, twelve original research articles are presented that dealt with different questions and the research models used within. The findings of Mocker and co-workers demonstrate that renal chemerin expression, a chemoattractant adipokine, is associated with processes of inflammation and fibrosis during renal damage [2]. The protection of kidney function by attenuating induced renal inflammation was shown with the use of Farnesiferol B, an agonist of a receptor that is expressed by renal tubular epithelial cells [1]. The xanthin oxidase inhibitor febuxostat is shown to exert anti-inflammatory action and protect against diabetic nephropathy development [3]. Kidney injury leading to focal segmental glomerulosclerosis was shown by variants in the collagen 4A5 g...

“…Pericytes implantation has been successful in repairing various tissues including muscle, heart, and brain [16,29,60,61]. Pericytes have also been implicated in promoting fibrosis in various tissues [36,37,55,62,63]. Studies by Birbrair et al suggest two populations of pericytes type 1 and type 2 [64].…”

Section: Discussionmentioning

confidence: 99%

Characterization of Burn Eschar Pericytes

Evdokiou

Kanisicak

Gierek

et al. 2020

JCM

Pericytes are cells that reside adjacent to microvasculature and regulate vascular function. Pericytes gained great interest in the field of wound healing and regenerative medicine due to their multipotential fate and ability to enhance angiogenesis. In burn wounds, scarring and scar contractures are the major pathologic feature and cause loss of mobility. The present study investigated the influence of burn wound environment on pericytes during wound healing. Pericytes isolated from normal skin and tangentially excised burn eschar tissues were analyzed for differences in gene and protein expression using RNA-seq., immunocytochemistry, and ELISA analyses. RNA-seq identified 443 differentially expressed genes between normal- and burn eschar-derived pericytes. Whereas, comparing normal skin pericytes to normal skin fibroblasts identified 1021 distinct genes and comparing burn eschar pericytes to normal skin fibroblasts identified 2449 differential genes. Altogether, forkhead box E1 (FOXE1), a transcription factor, was identified as a unique marker for skin pericytes. Interestingly, FOXE1 levels were significantly elevated in burn eschar pericytes compared to normal. Additionally, burn wound pericytes showed increased expression of profibrotic genes periostin, fibronectin, and endosialin and a gain in contractile function, suggesting a contribution to scarring and fibrosis. Our findings suggest that the burn wound environment promotes pericytes to differentiate into a myofibroblast-like phenotype promoting scar formation and fibrosis.