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Fibrosis as the Engine of Kidney Functional Decline: Donald W. Seldin Young Investigator Award Lecture.

Tubulointerstitial fibrosis is a defining histopathologic hallmark of CKD and develops in response to diverse acute and chronic insults to the kidney. Converging evidence has established interstitial fibrosis as a direct causal driver of kidney function decline. After injury, tubular epithelial cells can initiate fibrotic remodeling by promoting immune cell recruitment and myofibroblast activation. Myofibroblasts, predominantly derived from tissue-resident fibroblasts and pericytes to a lesser extent, are the principal effector cells of kidney interstitial fibrosis, producing the majority of e…

Ginsenoside Rh3 induces barrier-associated injury in an in vitro blood-brain barrier model with involvement of MMP2/9.

The blood-brain barrier (BBB) is essential for maintaining central nervous system homeostasis, and its disruption is associated with numerous neurological disorders. Ginsenoside Rh3 (GRh3), a bioactive saponin with recognized anticancer properties, has previously been shown to exert cytotoxic effects on neural cells, raising concerns regarding its neurovascular safety. In this study, we evaluated the effects of GRh3 in an in vitro co-culture transwell BBB model comprising mouse-derived bEnd.3 endothelial cells, pericytes, and C8-D1A astrocytic cells. Exposure to GRh3 (0.4-1.6 μM) for 24 h redu…

Identification and initial experimental assessment of DCLK3 as a potential sarcopenia biomarker: A multi-omics and machine learning approach.

Sarcopenia is an age-related condition marked by high prevalence and significant clinical consequences, underscoring the need for timely dia … LK3 in sarcopenia. snRNA-Seq and communication analysis further showed enriched DCLK3 expression in pericytes, with PDGF signaling as the major pathway mediating their crosstalk with other cells. These results position DCLK3 as a compelling diagnostic marker and therapeutic target, providing new insights into sarcopenia pathogenesis.

Identification of two distinct uveal melanoma subtypes based on the immune cell infiltration of the primary tumour.

BACKGROUND: Uveal melanoma (UM) is the most common intraocular malignancy, with poor prognosis in metastatic cases and limited response to c … Ligand-receptor analysis identified extensive interactions between these aggressive melanocytes and pericytes/macrophages. Flow cytometric analysis confirmed two distinct immune infiltrate profiles: low-infiltrate tumours dominated by CD14⁺ cells, and high-infiltrate tumours with CD8⁺ memory-like T cells expressing PD-1 and CD27. Stromal marker analysis rev …

A novel compound heterozygous variant in LAMA2 gene in a family with merosin-deficient congenital muscular dystrophy.

LAMA2 encodes the alpha-2 subunit of a protein called Laminin. It consists of three subunits Y; alpha, beta and gamma. Alpha2 subunit from LAMA2 gene along with beta-2 and gamma-2 forms laminin-2 protein. This protein is necessary for assembly of basement membrane in skeletal muscle cells, Schwann cells, astrocytes and pericytes. More than 100 LAMA2 variant identified so far which cause recessive form of muscular dystrophy (MD) either a severe form, congenital (CMD) or mild form, limb-girdle (LGMD). Patient with LAMA2 MD suffered from muscle weakness, elevated creatine kinase, facial dysmorphi…

Preserving blood-retinal barrier integrity: a path to retinal ganglion cell protection in glaucoma and traumatic optic neuropathy.

Retinal ganglion cells (RGCs) are the visual gateway of the brain, with their axons converging to form the optic nerve, making them the most vulnerable target in diseases such as glaucoma and traumatic optic neuropathy (TON). In both diseases, the disruption of the blood-retinal barrier(BRB) is considered an important mechanism that accelerates RGC degeneration and hinders axon regeneration. The BRB consists of the inner blood-retinal barrier (iBRB) and the outer blood-retinal barrier (oBRB), which are maintained by endothelial cells(ECs), pericytes(PCs), and retinal pigment epithelial (RPE), …

Дифференцированное выражение и модуляция ЭБИ2 и 7α,25-OHC синтезирующих (CH25H, CYP7B1) и унижающих достоинство (HSD3B7) ферментов в мышах и человеческих сосудистых клетках.

Внутренние лиганды рецептора EBI2, оксистерина 7α,25OHC, имеющие решающее значение для иммунной реакции, тщательно регулируются ферментами CH25H, CYP7B1 и HSD3B7. Линфоидные стромальные клетки и фолликулярные дендритические клетки внутри Т-клеток поддерживают градиент 7α,25OHC, при этом стромальные клетки увеличиваются, а дендритные клетки уменьшают их концентрацию. Этот градиент имеет ключевое значение для надлежащего размещения клеток В в лимфоидной ткани. В животной модели множественного склероза экспериментальный аутоиммунный энцефаломиэлит, уровни 7α,25OHC быстро увеличиваются в центральн

Совпадение в аннотации оригинала
The endogenous ligand for the EBI2 receptor, oxysterol 7α,25OHC, crucial for immune responses, is finely regulated by CH25H, CYP7B1 and HSD3 … hanges in their expression during inflammation. Ebi2 was abundantly expressed in endothelial cells, pericytes/smooth muscle cells, and astrocytic endfeet. Ch25h, Cyp7b1, and Hsd3b7 were variably detected in each cell type, suggesting their active involvement in oxysterol 7α,25OHC synthesis and gradient maintenance under normal conditions. Significant specie …

Argonaute 2 restored erectile function and corpus cavernosum mitochondrial function by reducing apoptosis in a mouse model of cavernous nerve injury.

PURPOSE: To determine whether the overexpression of the Argonaute RNA-induced silencing complex catalytic component 2 (Ago2) improves erecti … blot analysis showed that under Ago2 overexpressing conditions, the contents of endothelial cells, pericytes, and neuronal cells increased in the penile tissues of CNI mice, and this was attributed to reduced apoptosis and ROS production. In addition, we also found that Ago2 overexpression could restore penile mitochondrial function, thereby improving erec …

Molecular and Cellular Mechanisms Involved in the Pathophysiology of Retinal Vascular Disease-Interplay Between Inflammation and Oxidative Stress.

Retinal vascular diseases encompass several retinal disorders, including diabetic retinopathy, retinopathy of prematurity, age-related macul … tween angiopoietin 2 and the Tie2 receptor results in aberrant Tie2 signaling, resulting in loss of pericytes, neovascularization, and inflammation. Notch signaling and hypoxia-inducible factors in ischemic conditions induce pathological neovascularization and disruption of the blood-retina barrier. An increase in the pro-inflammatory cytokines-TNF-α, IL-1β …

Role of endothelial cells and angiotensin converting enzyme-II in COVID-19 and brain damages post-infection.

Severe acute respiratory syndrome coronavirus 2 (SARS CoV-2) causes coronavirus disease 2019 (COVID-19), which became a pandemic in late 2019 and early 2020. Apart from many other symptoms of this infection, such as loss of smell and taste, rashes, body aches, fatigue, and psychological and cardiac symptoms, it also causes vasodilation in response to inflammation via nitric oxide release. SARS CoV-2 affects microcirculation, resulting in the swelling and damage of endothelial cells, micro thrombosis, constriction of capillaries, and damage to pericytes that are vital for the integrity of capil…

Tunnelling nanotubes between neuronal and microglial cells allow bi-directional transfer of α-Synuclein and mitochondria.

Tunnelling Nanotubes (TNTs) facilitate contact-mediated intercellular communication over long distances. Material transfer via TNTs can range from ions and intracellular organelles to protein aggregates and pathogens. Prion-like toxic protein aggregates accumulating in several neurodegenerative pathologies, such as Alzheimer's, Parkinson's, and Huntington's diseases, have been shown to spread via TNTs not only between neurons, but also between neurons-astrocytes, and neurons-pericytes, indicating the importance of TNTs in mediating neuron-glia interactions. TNT-like structures were also report…

ARHGEF37 overexpression promotes extravasation and metastasis of hepatocellular carcinoma via directly activating Cdc42.

BACKGROUND: The extravasation capability of hepatocellular carcinoma (HCC) cells plays a vital role in distant metastasis. However, the unde … formation in HCC cells, which consequently disrupted the interaction between endothelial cells and pericytes. Importantly, treatment with ZCL278, a specific inhibitor of Cdc42, dramatically inhibited the attachment of ARHGEF37-overexpressing HCC cells to endothelial cells, and the adherence and extravasation in the lung alveoli, resulting in suppression of …

Neurovascular unit pathology is observed very early in disease progression in the mutant SOD1G93A mouse model of amyotrophic lateral sclerosis.

Amyotrophic lateral sclerosis (ALS) is a debilitating neurodegenerative disease characterized by motor neuron degeneration that causes neuro … ltrastructural observation revealed intact TJ. Additionally, thickened basement membrane, increased pericytes, and string vessels were observed. These alterations in neurovascular units and the vasculature are observed prior to reports of initial neuromuscular junction denervation. The identification of early pathogenesis may be critical to develop diagnost …

VEGFR1 signaling in retinal angiogenesis and microinflammation.

Five vascular endothelial growth factor receptor (VEGFR) ligands (VEGF-A, -B, -C, -D, and placental growth factor [PlGF]) constitute the VEG … c and inflammatory conditions, and it has been detected in retinal and choroidal endothelial cells, pericytes, retinal and choroidal mononuclear phagocytes (including microglia), Müller cells, photoreceptor cells, and the retinal pigment epithelium. Whilst the VEGF-A decoy function of VEGFR1 is well established, consequences of its direct signaling are less …

Arteriogenesis of the Spinal Cord-The Network Challenge.

Spinal cord ischemia (SCI) is a clinical complication following aortic repair that significantly impairs the quality and expectancy of life. … fferent cell types involved in adapting to stress, like endothelial cells, smooth muscle cells, and pericytes. This adaption to stress is subdivided in three phases-initiation, growth, and the maturation phase. In fields of endovascular aortic aneurysm repair, pre-operative selective segmental artery occlusion may enable the development of a sufficient coll …

Ischemia-Induced Multipotent Stem Cells Isolated from Stroke Patients Exhibit Higher Neurogenic Differentiation Potential than Bone Marrow-Derived Mesenchymal Stem Cells.

Perivascular areas of the brain harbor multipotent stem cells. We recently demonstrated that after a stroke, brain pericytes exhibit features of multipotent stem cells. Moreover, these ischemia-induced multipotent stem cells (iSCs) are present within ischemic areas of the brain of patients diagnosed with stroke. Although increasing evidence shows that iSCs have traits similar to those of mesenchymal stem cells (MSCs), the phenotypic similarities and differences between iSCs and MSCs remain unclear. In this study, we used iSCs extracted from stroke patients (h-iSCs) and compared their neurogeni…

Lipid-based nanoformulations in the treatment of neurological disorders.

The neurological disorders affect millions of people worldwide, and are bracketed as the foremost basis of disability-adjusted life years (DALYs). The treatment options are symptomatic and often the movement of drugs is restricted by a specialized network of endothelial cell layers (adjoined by tight cell-to-cell junction proteins; occludin, claudins, and junctional adhesion molecules), pericytes and astroglial foot processes. In recent years, advances in nanomedicine have led to therapies that target central nervous system (CNS) pathobiology via altering signaling mechanisms such as activatio…

Top ten discoveries of the year: Neurovascular disease.

The aim of this review is to highlight novel findings in 2019 in the area of neurovascular disease. Experimental studies have provided insig … he cellular level, studies showed that proper function of endothelial and mural cells, particularly pericytes, is crucial to ensure full endothelial differentiation and blood-brain barrier integrity. Moreover, recent discoveries support the existence of a homeostatic crosstalk between vascular cells and other neural cells, including neurons. Cerebrovascular …

Proteoglycans as miscommunication biomarkers for cancer diagnosis.

Cancer cells reside in a microenvironment comprising of fibroblasts, endothelial cells, pericytes, macrophages, and other immune cells. All these cells coevolve with the cancer cells into a clinically manifested tumor. The immune system of the host should eliminate the tumor but fails to do so until it develops into a deadly disease. Based on these facts, cancer is a system disorder caused by miscommunications among cancer cells, its microenvironment, and host immune system. Therefore, identifying communication-related biomarkers will be important for cancer diagnosis and treatment. Proteoglyc…

Hydropic leiomyoma: a distinct variant of leiomyoma closely related to HMGA2 overexpression.

Hydropic leiomyoma (HLM) is a variant of uterine leiomyoma with characteristic features of zonal distributions of edema, increased vasculari … ve tumor cells, and HLM with HMGA2 overexpression also showed CD34-positive tumor vessel-supporting pericytes. In contrast to usual-type leiomyoma with a high frequency of MED12 mutations, no MED12 mutations were found in any HLM. HLM showed increased pAKT activity, indicating a strong contribution of AKT pathway signaling in HLM promoting tumor growth. Our …