scholarly journals Tauroursodeoxycholic Acid Decreases Keloid Formation by Reducing Endoplasmic Reticulum Stress as Implicated in the Pathogenesis of Keloid

2021 ◽  
Vol 22 (19) ◽  
pp. 10765
Author(s):  
Sunje Kim ◽  
Seong Eun Lee ◽  
Shinae Yi ◽  
Sangmi Jun ◽  
Yoon-Sun Yi ◽  
...  
Keyword(s):  
Endoplasmic Reticulum ◽  
Er Stress ◽  
Stress Signaling ◽  
Electron Microscopic ◽  
Tauroursodeoxycholic Acid ◽  
Tissue Samples ◽  
Mitochondrial Oxidative Stress ◽  
Steroid Injections ◽  
Normal Tissues ◽  
Keloid Formation

Keloids are a common form of pathologic wound healing and are characterized by an excessive production of extracellular matrix. This study examined the major contributing mechanism of human keloid pathogenesis using transcriptomic analysis. We identified the upregulation of mitochondrial oxidative stress response, protein processing in the endoplasmic reticulum, and TGF-β signaling in human keloid tissue samples compared to controls, based on ingenuity pathway and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses. Electron microscopic examinations revealed an increased number of dysmorphic mitochondria and expanded endoplasmic reticulum (ER) in human keloid tissue samples than that in controls. Western blot analysis performed using human tissues suggested noticeably higher ER stress signaling in keloids than in normal tissues. Treatment with tauroursodeoxycholic acid (TUDCA), an ER stress inhibitor, significantly decreased scar formation in rabbit models, compared to normal saline and steroid injections. In summary, our findings demonstrate the contributions of mitochondrial dysfunction and dysregulated ER stress signaling in human keloid formation and the potential of TUDCA in the treatment of keloids.

Western diet induced nuclear NFATC1 activates pro-apoptotic endoplasmic reticulum (ER) stress signaling, and progresses NAFLD to NASH

2020 ◽  
Vol 73 ◽  
pp. S684-S685
Author(s):  
Muhammad Umair Latif ◽  
Kristina Reutlinger ◽  
Geske Schmidt ◽  
Sercan Mercan ◽  
Julia Kitz ◽  
...  
Keyword(s):  
Endoplasmic Reticulum ◽  
Er Stress ◽  
Western Diet ◽  
Stress Signaling

scholarly journals Aquaporin-11 Contributes to TGF-β1-induced Endoplasmic Reticulum Stress in Human Visceral Adipocytes: Role in Obesity-Associated Inflammation

Cells ◽  
2020 ◽  
Vol 9 (6) ◽  
pp. 1403 ◽  
Author(s):  
Gema Frühbeck ◽  
Inmaculada Balaguer ◽  
Leire Méndez-Giménez ◽  
Víctor Valentí ◽  
Sara Becerril ◽  
...  
Keyword(s):  
Endoplasmic Reticulum ◽  
Adipose Tissue ◽  
Er Stress ◽  
Subcutaneous Fat ◽  
Subcellular Fractionation ◽  
Normal Weight ◽  
Compensatory Mechanism ◽  
Tissue Samples ◽  
Water Glycerol ◽  
Tgf Β1

Aquaporin-11 (AQP11) is expressed in human adipocytes, but its functional role remains unknown. Since AQP11 is an endoplasmic reticulum (ER)-resident protein that transports water, glycerol, and hydrogen peroxide (H2O2), we hypothesized that this superaquaporin is involved in ER stress induced by lipotoxicity and inflammation in human obesity. AQP11 expression was assessed in 67 paired visceral and subcutaneous adipose tissue samples obtained from patients with morbid obesity and normal-weight individuals. We found that obesity and obesity-associated type 2 diabetes increased (p < 0.05) AQP11 mRNA and protein in visceral adipose tissue, but not subcutaneous fat. Accordingly, AQP11 mRNA was upregulated (p < 0.05) during adipocyte differentiation and lipolysis, two biological processes altered in the obese state. Subcellular fractionation and confocal microscopy studies confirmed its presence in the ER plasma membrane of visceral adipocytes. Proinflammatory factors TNF-α, and particularly TGF-β1, downregulated (p < 0.05) AQP11 mRNA and protein expression and reinforced its subcellular distribution surrounding lipid droplets. Importantly, the AQP11 gene knockdown increased (p < 0.05) basal and TGF-β1-induced expression of the ER markers ATF4 and CHOP. Together, the downregulation of AQP11 aggravates TGF-β1-induced ER stress in visceral adipocytes. Owing to its “peroxiporin” properties, AQP11 overexpression in visceral fat might constitute a compensatory mechanism to alleviate ER stress in obesity.

Liver Ultrastructural Pathology in Cocaine Users

1997 ◽  
Vol 3 (S2) ◽  
pp. 55-56
Author(s):  
H.J. Finol ◽  
D.D. Mondragón ◽  
Y.M. González ◽  
C. Paradisi ◽  
N. González ◽  
...  
Keyword(s):  
Endoplasmic Reticulum ◽  
Liver Function ◽  
Smooth Endoplasmic Reticulum ◽  
Liver Function Tests ◽  
Electron Microscopic Investigation ◽  
Electron Microscopic ◽  
Tissue Samples ◽  
Ultrastructural Pathology ◽  
Function Tests ◽  
Cocaine Users

Although liver function tests could be abnormal in humans taking cocaine the histopathological basis for this disorder has not been well established. Light microscopic studies have shown the existence of peripheral, centrilobular or diffuse necrosis. The only electron microscopic investigation we could find reports hepatocyte alterations including dilated rough endoplasmic reticulum, hypertrophy of smooth endoplasmic reticulum, and existence of phagolysosomes. In this work we report the liver ultrastructural pathology in chronic cocaine users.Liver biopsies were obtained in five male patients, 25-44 years old. These patients had consumed cocaine and other drugs (marihuana, alcohol, amphetamines, etc..) for 7-30 years. All of them had altered liver function tests. Tissue samples were processed with routine techniques for transmission electron microscopy and observed in a Hitachi H-500 electron microscope.Abnormalities observed included those previously reported as swollen rough and smooth endoplasmic reticulum, presence of autophagic vacuoles and lipid deposition.

scholarly journals Klotho Ameliorates Chemically Induced Endoplasmic Reticulum (ER) Stress Signaling

2013 ◽  
Vol 31 (4-5) ◽  
pp. 659-672 ◽  
Author(s):  
Srijita Banerjee ◽  
Yanhua Zhao ◽  
Partha S. Sarkar ◽  
Kevin P. Rosenblatt ◽  
Ronald G. Tilton ◽  
...  
Keyword(s):  
Endoplasmic Reticulum ◽  
Er Stress ◽  
Stress Signaling ◽  
Chemically Induced

scholarly journals The Interplay of Mitochondrial Oxidative Stress and Endoplasmic Reticulum Stress in Cardiovascular Fibrosis in Obese Rats

Antioxidants ◽  
2021 ◽  
Vol 10 (8) ◽  
pp. 1274
Author(s):  
Francisco V. Souza-Neto ◽  
Sara Jiménez-González ◽  
Beatriz Delgado-Valero ◽  
Raquel Jurado-López ◽  
Marie Genty ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Endoplasmic Reticulum ◽  
Er Stress ◽  
Control Diet ◽  
Ang Ii ◽  
Mitochondrial Oxidative Stress ◽  
Relevant Role ◽  
Male Wistar Rats ◽  
Cardiovascular Fibrosis ◽  
Stress Activation

We have evaluated the role of mitochondrial oxidative stress and its association with endoplasmic reticulum (ER) stress activation in the progression of obesity-related cardiovascular fibrosis. MitoQ (200 µM) was orally administered for 7 weeks to male Wistar rats that were fed a high-fat diet (HFD, 35% fat) or a control diet (CT, 3.5% fat). Obese animals presented cardiovascular fibrosis accompanied by increased levels of extracellular matrix proteins and profibrotic mediators. These alterations were associated with ER stress activation characterized by enhanced levels (in heart and aorta vs. CT group, respectively) of immunoglobulin binding protein (BiP; 2.1-and 2.6-fold, respectively), protein disulfide-isomerase A6 (PDIA6; 1.9-fold) and CCAAT-enhancer-binding homologous protein (CHOP; 1.5- and 1.8-fold, respectively). MitoQ treatment was able to prevent (p < 0.05) these modifications at cardiac and aortic levels. MitoQ (5 nM) and the ER stress inhibitor, 4-phenyl butyric acid (4 µM), were able to block the prooxidant and profibrotic effects of angiotensin II (Ang II, 10−6 M) in cardiac and vascular cells. Therefore, the data show a crosstalk between mitochondrial oxidative stress and ER stress activation, which mediates the development of cardiovascular fibrosis in the context of obesity and in which Ang II can play a relevant role.

scholarly journals Tauroursodeoxycholic Acid Protects Retinal Pigment Epithelial Cells from Oxidative Injury and Endoplasmic Reticulum Stress In Vitro

Biomedicines ◽  
2020 ◽  
Vol 8 (9) ◽  
pp. 367
Author(s):  
Reem Hasaballah Alhasani ◽  
Mohammad Almarhoun ◽  
Xinzhi Zhou ◽  
James Reilly ◽  
Steven Patterson ◽  
...  
Keyword(s):  
Endoplasmic Reticulum ◽  
Er Stress ◽  
Retinal Degeneration ◽  
Retinal Pigment Epithelial ◽  
Retinal Pigment ◽  
Tauroursodeoxycholic Acid ◽  
Antioxidant Genes ◽  
Rpe Cells ◽  
Pigment Epithelial

Retinal degeneration is characterized by the dysfunction of retinal cells. Oxidative and endoplasmic reticulum (ER) stress play an important role in the pathogenesis and progression of retinal degeneration. Tauroursodeoxycholic acid (TUDCA) has been demonstrated to have protective effects in in vitro and in vivo retinal degeneration models. To fully understand the molecular mechanisms of TUDCA’s protection, we first treated human retinal pigment epithelial (RPE) cells, ARPE-19, with H2O2 or H2O2 plus TUDCA for 24 h. RPE cells co-exposed to TUDCA had higher cell viability and lower cell death rate compared to cells exposed to H2O2 alone. TUDCA significantly increased antioxidant capacity in H2O2-treated RPE cells by decreasing the generation of reactive oxygen species (ROS) and Malondialdehyde (MDA), upregulating the expression of antioxidant genes, and increasing the generation of glutathione (GSH). TUDCA also inhibited inflammation in H2O2-challenged RPE cells by decreasing the expression of proinflammatory cytokines. Furthermore, TUDCA suppressed thapsigargin-induced ER stress in RPE cells, as demonstrated by decreased the expression of CCAAT-enhancer-binding protein homologous protein (CHOP) and apoptosis. Our present study suggests that TUDCA can protect RPE cells against oxidative damage, inflammation, and ER stress and may benefit patients with retinal degeneration.

RyR1-mediated moderate endoplasmic reticulum stress is required for myogenic differentiation of myoblasts

2021 ◽  
Author(s):  
Kai Qiu ◽  
Yubo Wang ◽  
Doudou Xu ◽  
Linjuan He ◽  
Xin Zhang ◽  
...  
Keyword(s):  
Endoplasmic Reticulum ◽  
Er Stress ◽  
Cell Fate ◽  
Muscle Development ◽  
Myogenic Differentiation ◽  
C2c12 Cells ◽  
Stress Signaling ◽  
Congenital Myopathies ◽  
Myotube Formation

Abstract BackgroundCytosolic Ca2+ plays vital roles in myogenesis and muscle development. Key mutations of ryanodine receptor 1 (RyR1), a major Ca2+ release channel of endoplasmic reticulum (ER), are main causes of severe congenital myopathies. The role of RyR1 in myogenic differentiation has attracted intense research interest, however, it remains unclear. MethodsThis study employed RyR1-knockdown myoblasts and CRISPR/Cas9-based RyR1-knockout myoblasts cells to explore the role of RyR1 in myogenic differentiation, myotube formation as well as the potential mechanism of RyR1-related myopathies.ResultsCytoplasmic Ca2+ concentration was significantly elevated during myogenic differentiation of both primary myogenic cells and myoblasts C2C12 cells, accompanied with a dramatic increase in RyR1 expression and resultant ER stress. Inhibition of RyR1 by siRNA-mediated silence or chemical inhibitor, dantrolene, significantly reduced cytosolic Ca2+, alleviated ER stress, and blocked multinucleated myotube formation. Moderate activation of ER stress effectively relieved myogenic differentiation stagnation induced by RyR1 suppression and demonstrated that RyR1 modulates myogenic differentiation via activation of Ca2+ -induced ER stress signaling. RyR1 knockout-induced Ca2+ leakage led to severe ER stress and excessive unfolded protein response, and drove cell fate from differentiation into apoptosis. ConclusionsTherefore, we concluded that dramatic increase in RyR1 expression is required for myogenic differentiation, and RyR1-mediated Ca2+ release leading to the activation of ER stress signaling serves a double-edged sword role during myogenic differentiation. This study contributes to a novel understanding of the role of RyR1 in muscle development and related congenital myopathies, and provides a potential target for regulation of muscle regeneration and tissue engineering.

Sign in / Sign up

Export Citation Format

Share Document