Stellate cells storing retinol in the liver of adult lamprey,Lampetra japonica

Summary Distribution, localization and fine structure of the stellate cells in the liver of lamprey, Lampetra japonica, were studied during the spawning migration by use of Kupffer's gold-chloride method, fluorescence microscopy for vitamin A (retinol) and electron microscopy. The stellate cells in the lamprey liver differ in some of their properties from those in mammalian livers. Stellate cells which store abundant retinol in lipid droplets, occur not only in the hepatic parenchyma, but also in the dense perivascular and capsular connective tissue of the liver and in the interstitium of pancreatic tissue. In the hepatic parenchyma these cells are located perisinusoidally or along thick bundles of collagen fibrils. The stellate cells display a number of large retinol-containing lipid droplets, granular endoplasmic reticulum, tubular structures, dense bodies, Golgi complex, microtubules, and microfilaments. In the space of Disse, the stellate cells and extracellular fibrilar components such as collagen fibrils and microfibrils (11–12 nm in diameter) are intervened between the two layers of basal laminae. Differentiation and possible functions of the stellate cells in the lamprey liver are discussed.     

An analysis of the association between various synaptic parameters during cortical development

Summary Stellate cells in the rabbit adenohypophysis were observed electron microscopically under normal and experimental conditions such as lactation, thyroidectomy, adrenalectomy, or castration.In control animals stellate cells had a scanty cytoplasm surrounding the nucleus and possessed slender processes extending between granulated cells. The processes were interconnected by desmosomes to form a meshwork. In the cytoplasm, abundant microfilaments were present as well as ill-developed ordinary cell organelles, but secretory granules were absent.In the adenohypophysis of experimental groups, in which the granulated cells underwent characteristic changes, stellate cells also showed remarkable morphological alterations which were similar in all groups. In general, they became hypertrophied, and contained a well-developed Golgi apparatus and rough-surfaced endoplasmic reticulum. Lysosomes or lipid droplets were frequently encountered. Between adjacent stellate cells, intercellular canals were markedly developed and many microvilli were noticed.Based on the above data, it is suggested that the stellate cells are not only sustentacular elements, but play an important role in the function of the adenohypophysis, such as the supply of materials to granulated cells or the disposal of waste products.This investigation was supported in part by the Ministry of Education, Science and Culture, Japan     

Specific paracrystalline structures of rough endoplasmic reticulum in the follicular (stellate) cells of the dog adenohypophysis

Summary The fine structure of follicular cells of the adenohypophysis was examined in fetal, neonatal, and adult beagle dogs. Prior to birth, undifferentiated follicular cells are common. At birth mature cells that form follicles are routinely encountered. The fine structural appearance of follicular cells is unchanged between birth and adulthood. Follicular cells of puppies and adults are, however, distinguished by the presence of unusual complexes within distended cisternae of the rough endoplasmic reticulum. These complexes vary greatly in morphology, some appear as a maze of interconnecting tubules while others show a highly organized paracrystalline configuration. The presence of these paracrystalloid structures in follicular cells supports the view that they represent a distinct pituitary cell type.Supported by NIH Grants AM19743 and NS12969The authors wish to thank John Patrikes and Helen Mantulin for their expert technical assistance     

Proteome Variations in Pancreatic Stellate Cells upon Stimulation with Proinflammatory Factors

Pancreatic stellate cells are key mediators in chronic pancreatitis and play a central role in the development of pancreatic fibrosis, stromal formation, and progression of pancreatic cancer. This study was aimed at investigating molecular changes at the level of the proteome that are associated with the activation of pancreatic stellate cells by proinflammatory factors, namely TNF-α, FGF2, IL6, and chemokine (C-C motif) ligand 4 (CCL4). They were added individually to cells growing in serum-free medium next to controls in medium supplemented with serum, thus containing a mixture of them all, or in serum-free medium alone. Variations were detected by means of a microarray of 810 antibodies targeting relevant proteins. All tested factors triggered increased proliferation and migration. Further analysis showed that TNF-α is the prime factor responsible for the activation of pancreatic stellate cells. CCL4 is associated with cellular neovascularization, whereas FGF2 and IL6 induction led to better cellular survival and decreased apoptotic activity of the stellate cells. The identified direct effects of individual cytokines on human pancreatic stellate cells provide new insights about their contribution to pancreatic cancer promotion.     

LncRNA NONRATT021972 involved the pathophysiologic processes mediated by P2X<Subscript>7</Subscript> receptors in stellate ganglia after myocardial ischemic injury

Adenosine triphosphate (ATP) acts on P2X receptors to initiate signal transmission. P2X₇ receptors play a role in the pathophysiological process of myocardial ischemic injury. Long noncoding RNAs (lncRNAs) participate in numerous biological functions independent of protein translation. LncRNAs are implicated in nervous system diseases. This study investigated the effects of NONRATT021972 small interference RNA (siRNA) on the pathophysiologic processes mediated by P2X₇ receptors in stellate ganglia (SG) after myocardial ischemic injury. Our results demonstrated that the expression of NONRATT021972 in SG was significantly higher in the myocardial ischemic (MI) group than in the control group. Treatment of MI rats with NONRATT021972 siRNA, the P2X₇ antagonist brilliant blue G (BBG), or P2X₇ siRNA improved the histology of injured ischemic cardiac tissues and decreased the elevated concentrations of serum myocardial enzymes, creatine kinase (CK), CK isoform MB (CK-MB), lactate dehydrogenase (LDH) and aspartate aminotransferase (AST) compared to the MI rats. NONRATT021972 siRNA, BBG, or P2X₇ siRNA treatment in MI rats decreased the expression levels of P2X₇ immunoreactivity, P2X₇ messenger RNA (mRNA), and P2X₇ protein, interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), and phosphorylated p38 mitogen-activated protein kinase (p38 MAPK) in the SG compared to MI rats. NONRATT021972 siRNA treatment prevented the pathophysiologic processes mediated by P2X₇ receptors in the SG after myocardial ischemic injury.     

The kinin receptor is expressed in the Malpighian tubule stellate cells in the mosquito Aedes aegypti (L.): a new model needed to explain ion transport?

It is known that insect kinins increase diuresis and fluid secretion in the Aedes aegypti Malpighian tubule, causing a rapid drop of the transepithelial resistance and increasing chloride conductance from the hemolymph towards the tubule lumen. The tubule is composed of both principal and stellate cells. The main route for increased chloride influx upon kinin treatment is proposed to be paracellular, with septate junctions acquiring increased chloride selectivity and conductance. Therefore, kinin treatment renders the Ae. aegypti tubule a “leaky epithelium”, and under this model the kinin receptor is postulated to be expressed in principal cells. However, in another dipteran, the fruit fly Drosophila melanogaster, the main route for chloride transport is transcellular through stellate cells. In both the fruit fly and the mosquito Anopheles stephensi the kinin receptor has been immunolocalized in stellate cells, where it regulates transepithelial chloride permeability. Here we show that in Ae. aegypti, similarly, the stellate cells express the kinin receptor. This was confirmed through immunohistochemistry with two specific anti-kinin receptor antibodies and confocal analysis. The receptor is detected as a 75 kDa band in western blot. These results indicate that the currently accepted model for chloride transport must be re-evaluated in Ae. aegypti and suggest the kinin regulatory signals controlling intercellular junctions originate in the stellate cells.     

Inhibition of EGFR attenuates fibrosis and stellate cell activation in diet-induced model of nonalcoholic fatty liver disease

Nonalcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease. NAFLD begins with steatosis and advances to nonalcoholic steatohepatitis (NASH) and cirrhosis. The molecular mechanisms involved in NAFLD progression are not understood. Based on recent studies showing dysregulation of epidermal growth factor receptor (EGFR) in animal models of liver injury, we sought to determine if inhibition of EGFR mitigates liver fibrosis and HSC activation in NAFLD. We utilized the high fat diet (HFD)-induced murine model of liver injury to study the role of EGFR in NAFLD. The lipid accumulation, oxidative stress, hepatic stellate cell (HSC) activation and matrix deposition were examined in the liver tissues. We also evaluated the EGFR signaling pathway, ROS activation and pro-fibrogenic phenotype in oxidized low density lipoproteins (ox-LDL) challenged cultured HSCs. We demonstrate that EGFR was phosphorylated in liver tissues of HFD murine model of NAFLD. Inhibition of EGFR prevented diet-induced lipid accumulation, oxidative stress, and HSC activation and matrix deposition. In cultured HSCs, we show that ox-LDL caused rapid activation of the EGFR signaling pathway and induce the production of reactive oxygen species. EGFR also mediated HSC activation and promoted a pro-fibrogenic phenotype. In conclusion, our data demonstrate that EGFR plays an important role in NAFLD and is an attractive target for NAFLD therapy.