Presence Of Fenestrae Research Articles

Liver sinusoidal endothelial cell: An important yet often overlooked player in the liver fibrosis.

Liver sinusoidal endothelial cells (LSECs) are liver-specific endothelial cells with the highest permeability than other mammalian endothelial cells, characterized by the presence of fenestrae on their surface, the absence of diaphragms and the lack of basement membrane. Located at the interface between blood and other liver cell types, LSECs mediate the exchange of substances between the blood and the Disse space, playing a crucial role in maintaining substance circulation and homeostasis of multicellular communication. As the initial responders to chronic liver injury, the abnormal LSEC activation not only changes their own physicochemical properties but also interrupts their communication with hepatic stellate cells and hepatocytes, which collectively aggravates the process of liver fibrosis. In this review, we have comprehensively updated the various pathways by which LSECs were involved in the initiation and aggravation of liver fibrosis, including but not limited to cellular phenotypic change, the induction of capillarization, decreased permeability and regulation of intercellular communications. Additionally, the intervention effects and latest regulatory mechanisms of anti-fibrotic drugs involved in each aspect have been summarized and discussed systematically. As we studied deeper into unraveling the intricate role of LSECs in the pathophysiology of liver fibrosis, we unveil a promising horizon that pave the way for enhanced patient outcomes.

Isolation and Characterization of Mouse Primary Liver Sinusoidal Endothelial Cells.

Liver sinusoidal endothelial cells (LSECs) are specialized endothelial cells located at the interface between the circulation and the liver parenchyma. LSECs have a distinct morphology characterized by the presence of fenestrae and the absence of basement membrane. LSECs play essential roles in many pathological disorders in the liver, including metabolic dysregulation, inflammation, fibrosis, angiogenesis, and carcinogenesis. However, little has been published about the isolation and characterization of the LSECs. Here, this protocol discusses the isolation of LSEC from both healthy and nonalcoholic fatty liver disease (NAFLD) mice. The protocol is based on collagenase perfusion of the mouse liver and magnetic beads positive selection of nonparenchymal cells to purify LSECs. This study characterizes LSECs using specific markers by flow cytometry and identifies the characteristic phenotypic features by scanning electron microscopy. LSECs isolated following this protocol can be used for functional studies, including adhesion and permeability assays, as well as downstream studies for a particular pathway of interest. In addition, these LSECs can be pooled or used individually, allowing multi-omics data generation including RNA-seq bulk or single cell, proteomic or phospho-proteomics, and Assay for Transposase-Accessible Chromatin using sequencing (ATAC-seq), among others. This protocol will be useful for investigators studying LSECs' communication with other liver cells in health and disease and allow an in-depth understanding of the role of LSECs in the pathogenic mechanisms of acute and chronic liver injury.

Taxonomy and diversity of a little-known diatom genus Simonsenia (Bacillariaceae) in the marine littoral: novel taxa from the Yellow Sea and the Gulf of Mexico

Background and aims – The diatom genus Simonsenia has been considered for some time a minor taxon, limited in its distribution to fresh and slightly brackish waters. Recently, knowledge of its diversity and geographic distribution has been enhanced with new species described from brackish-marine waters of the southern Iberian Peninsula and from inland freshwaters of South China, and here we report novel Simonsenia from fully marine waters.
 Methods – New isolates of Simonsenia species were obtained from marine waters, the littoral zone of the Korean Yellow Sea coast and the Gulf of Mexico in Corpus Christi (Texas), and documented in LM, SEM and with DNA sequence data (plastid-encoded rbcL and psbC). Phylogenetic trees of raphid diatoms were constructed to assess the relationships of the new species and of the genus as a whole.
 Key results and conclusions – Two novel species of Simonsenia (S. eileencoxiae and S. paucistriata) are described and a further putative taxon is characterized morphologically. The molecular phylogeny of the new Simonsenia species and previously sequenced species supports both the monophyly of the genus and its place within the Bacillariaceae. The Simonsenia clade clusters with clades composed of Cylindrotheca, Denticula and some Nitzschia spp. (including N. amphibia, N. frustulum, N. inconspicua). Hence Simonsenia is firmly positioned within the Bacillariaceae by molecular phylogenies, confirming its position within this group based on the possession of a canal raphe and its ultrastructure, and rejecting its classification within the Surirellaceae. Morphological data from the new Simonsenia species is typical for the genus, with a “simonsenioid” canal raphe type supported over the valve face with fenestral braces, alar canals connecting the canal raphe with the cell lumen, and the presence of fenestrae between the alar canals externally. Our results indicate unequivocally that the biogeography and the biodiversity of Simonsenia remain highly underestimated.

Three‐dimensional organization of fenestrae labyrinths in liver sinusoidal endothelial cells

Liver sinusoidal endothelial cell (LSEC) fenestrae are membrane-bound pores that are grouped in sieve plates and act as a bidirectional guardian in regulating transendothelial liver transport. The high permeability of the endothelial lining is explained by the presence of fenestrae and by various membrane-bound transport vesicles. The question as to whether fenestrae relate to other transport compartments remains unclear and has been debated since their discovery almost 40 years ago. In this study, novel insights concerning the three-dimensional (3D) organization of the fenestrated cytoplasm were built on transmission electron tomographical observations on isolated and cultured whole-mount LSECs. Classical transmission electron microscopy and atomic force microscopy imaging was performed to accumulate cross-correlative structural evidence. The data presented here indicate that different arrangements of fenestrae have to be considered: i.e. open fenestrae that lack any structural obstruction mainly located in the thin peripheral cytoplasm and complexes of multifolded fenestrae organized as labyrinth-like structures that are found in the proximity of the perinuclear area. Fenestrae in labyrinths constitute about one-third of the total LSEC porosity. The 3D reconstructions also revealed that coated pits and small membrane-bound vesicles are exclusively interspersed in the non-fenestrated cytoplasmic arms.

Fenestrated capillaries in subarachnoid space in the caudal spinal cord of the premature rat: an electron microscopic observation

The fine structure of the corms medullaris of the spinal cord and surrounding structures were studied in postnatal developing rats, with special attention being paid to the vasculature. The most striking finding was the presence of fenestrae in the capillary endothelium of the subarachnoid space. These structures were not obvious in adult rats. The fenestrated capillaries may influence fluid dynamics in the subarachnoid space of the spinal cord at the level of the conus medullaris, during early stage of postnatal development.

An electron microscopic study of the passage of colloidal particles from the blood vessels of the ciliary processes and choroid plexus of the rabbit.

The thinnest areas of the capillaries of the choroid plexus and ciliary processes in the eye of the rabbit are characterized by the presence of fenestrae. When various colloidal particles opaque to the electron beam (thorotrast, gold sol, and saccharated iron oxide) were injected into the blood stream, none were found in fenestrae or in areas that might suggest their having passed through fenestrae. The passage of marker particles from the lumen to the surrounding connective tissue does take place on occasion in the areas of thicker walls in the capillaries and venules rather than in the attenuated and fenestrated endothelial walls. The pathway taken by these markers may be either through the cytoplasm of the endothelial cells via membrane-bounded vesicles and vacuoles or through the intercellular spaces of the vessels. An altered aqueous humor (cloudy and plasmoid) was produced by endotoxin injection or by making a draining fistula in rabbit cornea. Both methods gave rise to the same changes in the blood vessels of the ciliary processes. Under such conditions of inflammation the passage of colloidal particles through the thicker walls of the capillaries and venules was greatly increased and occurred primarily as an intercellular passage between the endothelial cells. The attenuated and fenestrated areas of the endothelium of the small capillaries remained unchanged with no particles passing through them. These results on the altered vessels of the ciliary processes parallel those of Majno and Palade (26) on the rat cremaster muscle.