Matricellular Protein Thrombospondins: Influence on Ocular Angiogenesis, Wound Healing and Immuneregulation

Masli, Sharmila; Cursiefen, Claus; Zieske, James D.

doi:10.3109/02713683.2013.877936

Cited by 45 publications

(43 citation statements)

References 99 publications

(138 reference statements)

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“…3 ) as well as enzymes involved in ECM remodeling, including metalloproteases (Mmp1a, Mmp2, and Mmp13), protease inhibitors [Timp1 and Timp2, serine protease inhibitors (serpine1 suppress Thbs1 expression in adipose tissue ( 65 ). Thbs2, in contrast, attenuates fi brosis ( 67,68 ). We are unaware of reports documenting effects of dietary PUFA on Thbs2 expression.…”

Section: Ecm Remodeling Enzymesmentioning

confidence: 99%

Docosahexaenoic acid attenuates Western diet-induced hepatic fibrosis in Ldlr mice by targeting the TGFβ-Smad3 pathway

Lytle

Depner

Wong

et al. 2015

Journal of Lipid Research

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This article is available online at http://www.jlr.org mainly as neutral lipids consisting of triacylglycerols, cholesterol esters, and diacylglycerols. NAFLD ranges in severity from benign hepatosteatosis to nonalcoholic steatohepatitis (NASH) ( 1 ). NASH is defi ned as hepatosteatosis with infl ammation and hepatic injury ( 2 ). Although simple hepatosteatosis is considered clinically benign, NASH is the progressive form of the disease that can lead to significant changes in hepatic morphology (hepatocyte ballooning) and injury (cell death and fi brosis).The incidence of NAFLD has increased in parallel with the obesity epidemic in Western societies. In the general population, the prevalence of NAFLD is estimated to range from 6 to 33% ( 3 ), and ‫ف‬ 30-40% of individuals with hepatic steatosis progress to NASH ( 4 ). The prevalence of NASH ranges from 3 to 5% in the general population ( 3 ). NAFLD and NASH have high prevalence ( у 60%) in patients with type 2 diabetes ( 5 ). Additionally, NASH patients have higher mortality rates than NAFLD patients ( 6-8 ), and over a 10 year period, cirrhosis and liver-related death occurs in 20 and 12% of NASH patients, respectively ( 9 ). Because NASH can progress to cirrhosis, hepatocellular cancer, and liver failure ( 4,(10)(11)(12)(13)(14), it is the third most common cause for liver transplantation. NASH is projected to be the leading cause of liver transplantation in the United States by 2020 ( 15 ).Hepatic fi brosis involves the increased production of extracellular matrix (ECM) from activated hepatic stellate cells and myofi broblasts infi ltrating the liver. The liver has an underlayment of connective tissue composed of several Nonalcoholic fatty liver disease (NAFLD) is a signifi cant public health burden in Western societies. NAFLD is defi ned as excess accumulation of liver fat (hepatosteatosis),

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Section: Ecm Remodeling Enzymesmentioning

confidence: 99%

Docosahexaenoic acid attenuates Western diet-induced hepatic fibrosis in Ldlr mice by targeting the TGFβ-Smad3 pathway

Lytle

Depner

Wong

et al. 2015

Journal of Lipid Research

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“…TSP1 is a large matricellular protein found both intra- and extracellularly (Resovi et al, 2014). Multiple domains of TSP1 allow its interactions with cell surface receptors, growth factors, cytokines, or extracellular matrix proteins thereby supporting a variety of functions within the cell including modulation of cell migration, proliferation, and cell death (Masli et al, 2014). Therefore, TSP1 can regulate both extracellular and intracellular signaling complexes.…”

Section: Introductionmentioning

confidence: 99%

Alteration in cellular turnover and progenitor cell population in lacrimal glands from thrombospondin 1 −/− mice, a model of dry eye

Shatos

Hodges

Morinaga

et al. 2016

Experimental Eye Research

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The purpose of this study was to investigate the changes that occur in the lacrimal glands (LGs) in female thrombospondin 1 knockout (TSP1−/−) mice, a mouse model of the autoimmune disease Sjogren’s syndrome. The LGs of 4, 12, and 24 week-old female TSP1−/− and C57BL/6J (wild type, WT) mice were used. qPCR was performed to measure cytokine expression. To study the architecture, LG sections were stained with hematoxylin and eosin. Cell proliferation was measured using bromo-deoxyuridine and immunohistochemistry. Amount of CD47 and stem cell markers was analyzed by western blot analysis and location by immunofluorescence microscopy. Expression of stem cell transcription factors was performed using Mouse Stem Cell Transcription Factors RT2 Profiler PCR Array. Cytokine levels significantly increased in LGs of 24 week-old TSP1−/− mice while morphological changes were detected at 12 weeks. Proliferation was decreased in 12 week-old TSP1−/− mice. Three transcription factors were overexpressed and eleven underexpressed in TSP1−/− compared to WT LGs. The amount of CD47, Musashi1, and Sox2 was decreased while the amount of ABCG2 was increased in 12 week-old TSP1−/− mice. We conclude that TSP1 is necessary for maintaining normal LG homeostasis. Absence of TSP1 alters cytokine levels and stem cell transcription factors, LG cellular architecture, decreases cell proliferation, and alters amount of stem cell markers.

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“…17 The role of TSP-1 in the ocular surface as a modulator in avascular repair and immunoregulation has been reviewed. 18,19 On the other hand, CD36 is involved in diverse processes in the ocular surface, including angiogenesis, inflammation, and oxidative stress scavenging, depending on the ligands with which CD36 can interact. 20,21 The notion that both TSP-1 and CD36 are critical for ocular surface homeostasis has recently arisen as TSP-1 and CD36-deficient goblet cells have been reported as incapable of activating their endogenous TGF-b2.…”

Section: Introductionmentioning

confidence: 99%

Inflammatory Cytokine-Mediated Regulation of Thrombospondin-1 and CD36 in Conjunctival Cells

Soriano-Romaní

Contreras-Ruiz

García-Posadas

et al. 2015

Journal of Ocular Pharmacology and Therapeutics

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Purpose: Increased expression of transforming growth factor-b2 (TGF-b2) is reported in the conjunctiva of dry eye patients with no increase of anti-inflammatory activity of TGF-b2. Our aim was to compare the expression of molecules involved in TGF-b2 activation, thrombospondin-1 (TSP-1) and CD36, during murine and human conjunctival inflammation. Methods: Human conjunctival tissue from cadaveric donors, human conjunctival epithelial primary cells and fibroblasts, and murine conjunctivas were immunostained for TSP-1, CD36, or TGF-b2. Inflamed conjunctival tissues were obtained from C57BL/6 wild-type (WT) mice induced to develop experimental dry eye (EDE) with 10 days of desiccating conditions and scopolamine injections and TSP-1-deficient (TSP1 -/ -) mice, which spontaneously develop Sjögren's syndrome-associated conjunctival inflammation with age. Immunostaining intensities were compared using ImageJ software. Cultures of human conjunctival fibroblasts were stimulated with IL-1b and both secreted protein and message levels of TSP-1, CD36, and TGF-b2 were analyzed. Results: TSP-1 and CD36 were detectable in human and murine conjunctival tissues as well as primary conjunctival epithelial cells and fibroblasts. Increased conjunctival immunostaining of TGF-b2 and reduced CD36 were detected in EDE mice compared with WT mice. Interestingly, increased TGF-b2 and CD36 conjunctival immunostaining was detected in TSP1-/ -mice. The expression of TSP-1 and CD36 was downregulated in IL-1b-stimulated conjunctival fibroblasts at both the protein and message level, while active TGFb2 was undetected. Conclusions: The absence or reduced expression of either of the molecules involved in TGF-b2 activation supports proinflammatory conditions in the conjunctiva. Changes in TSP-1 and CD36 may serve as potential biomarkers of conjunctival inflammation.

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Matricellular Protein Thrombospondins: Influence on Ocular Angiogenesis, Wound Healing and Immuneregulation

Cited by 45 publications

References 99 publications

Docosahexaenoic acid attenuates Western diet-induced hepatic fibrosis in Ldlr mice by targeting the TGFβ-Smad3 pathway

Docosahexaenoic acid attenuates Western diet-induced hepatic fibrosis in Ldlr mice by targeting the TGFβ-Smad3 pathway

Alteration in cellular turnover and progenitor cell population in lacrimal glands from thrombospondin 1 −/− mice, a model of dry eye

Inflammatory Cytokine-Mediated Regulation of Thrombospondin-1 and CD36 in Conjunctival Cells

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