TSG-6 Controls Transcription and Activation of Matrix Metalloproteinase 1 in Conjunctivochalasis

Guo, Ping; Zhang, Suzhen; He, Hua; Zhu, Yingting; Tseng, Scheffer C.G.

doi:10.1167/iovs.11-8738

Cited by 17 publications

(12 citation statements)

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“…7). Because apoptosis of conjunctival fibroblasts was another hallmark of CCh, 18 the above finding also suggested the role of PTX3 in controlling the homeostasis of the conjunctival stroma. Because Aprotinin, Batimastat, and NNGH all helped rescue both fibroblasts from such cell death caused by PTX3 knockdown, overexpression of actMMP-1 and actMMP3 likely played an important causative role.…”

Section: Discussionmentioning

confidence: 85%

“…6). Thus, similar to TSG-6, 18 perturbation of PTX3 expression might be involved in pathogenesis of CCh in reference to activation of MMP-1. As to whether PTX-3 might be involved in regulating pathogenesis of CCH through other MMPs, it is a subject of current investigation in our lab.…”

Section: Discussionmentioning

confidence: 94%

“…13,[15][16][17] We have recently discovered that TSG-6 is constitutively expressed by human normal conjunctival epithelial tissue, is overexpressed in normal conjunctival fibroblasts under stimulation of TNF-a or IL-1b, and exerts an anti-inflammatory function by halting activation of MMP-1 and MMP-3 and apoptosis of CCh conjunctival fibroblasts. 18 Because in PTX3 null mice disclose that PTX3 has a cardioprotective role in acute myocardial infarction 19 and an atheroprotective effect, 20 we wondered whether PTX3 might also play an anti-inflammatory role similar to TSG-6 in CCh. Herein, we provide strong experimental evidence supporting the notion that PTX3 suppresses inflammation and apoptosis of conjunctival fibroblasts by inhibiting gene transcription and activation of MMP-1 and MMP-3 to combat the development of CCh.…”

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confidence: 99%

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PTX3 Controls Activation of Matrix Metalloproteinase 1 and Apoptosis in Conjunctivochalasis Fibroblasts

Guo

Zhang

et al. 2012

Invest. Ophthalmol. Vis. Sci.

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PURPOSE. Conjunctivochalasis (CCh) is an age-related inflammatory ocular surface disease manifesting redundant, loose conjunctiva folds. The pathogenic role of Pentraxin 3 (PTX3) in controlling upregulation of matrix metalloproteinase 1 (MMP-1) and MMP-3 in CCh remains undefined.METHODS. Cytolocation of PTX3 and apoptosis were compared by immunostaining and terminal deoxyribonucleotidyl transferase-mediated FITC-linked dUTP nick-end DNA labeling (TUNEL) assay between normal and CCh specimens containing the conjunctiva and the Tenon. Second to third cultures of normal and CCh fibroblasts were treated with or without Aprotinin, Batimastat, or N-isobutyl-N-(4-methoxyphenylsulfonyl)-glycylhydroxamic acid (NNGH), followed by transfection with or without PTX3 siRNA, and TNF-a or IL-1b. Cell lysates and culture media were collected to assess apoptosis measured by the Cell Death Detection ELISA and expression of PTX3, MMP-1, and MMP-3 transcripts and proteins by quantitative RT-PCR and Western blot, respectively. RESULTS. PTX3 immunostaining was negative in normal specimens, but strongly positive in the subconjunctival stroma of CCh specimens. More apoptotic cells were found in CCh samples than in normal specimens. Expression of PTX3 transcripts and protein was not constitutive in resting normal fibroblasts but was in resting CCh fibroblasts and was upregulated by IL-1b in both cell lysates and culture media of both fibroblasts. PTX3 siRNA further upregulated MMP-1 and MMP-3 transcripts in resting normal fibroblasts, but synergistically with IL-1b upregulated the expression of MMP-1 and MMP-3 transcripts only in CCh fibroblasts, with activation of MMP-1 more so than MMP-3. PTX3 siRNA knockdown also promoted cell death characterized by apoptosis and necrosis, and such cell death could be rescued by inhibitors against serine proteinase, MMP1, or MMP3.CONCLUSIONS. Perturbation of PTX3 expression might partake in apoptosis and pathogenesis of CCh by upregulating expression of MMP-1 and MMP-3, and activation of MMP-1 and MMP-3.

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Section: Discussionmentioning

confidence: 85%

Section: Discussionmentioning

confidence: 94%

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confidence: 99%

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PTX3 Controls Activation of Matrix Metalloproteinase 1 and Apoptosis in Conjunctivochalasis Fibroblasts

Guo

Zhang

et al. 2012

Invest. Ophthalmol. Vis. Sci.

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“…Erdogan-Poyraz et al17 reported that inflammatory cytokine interleukin (IL)-6 and IL-8 levels were correlated with the severity of CCh. Guo et al18 found that pentraxin 3 immunostaining was strongly positive in the subconjunctival stroma of CCh specimens. They stated that pentraxin 3 expression might partake in apoptosis and pathogenesis of CCh by upregulating expression of matrix metalloproteinase-1 (MMP-1) and matrix metalloproteinase-3 (MMP-3).…”

Section: Discussionmentioning

confidence: 99%

Clinical characteristics of patients with conjunctivochalasis

Balcı¹

2014

OPTH

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PurposeTo evaluate the clinical characteristics of patients with conjunctivochalasis (CCh).Methods and materialsThis retrospective study enrolled 30 subjects diagnosed with conjunctivochalasis. Complete ophthalmic examination, including visual acuity assessment, slit-lamp examination, applanation tonometry, dilated funduscopy, tear break-up time, Schirmer 1 test, and fluorescein staining were performed in all patients. Age, sex, laterality, ocular history, symptoms, and clinical findings were recorded.ResultsThe study included 50 eyes from 30 cases. Ages ranged from 45 to 80 years, with a mean age of 65±10 years. CChs grading were as follows: 30 (60%) eyes with grade 1 CCh; 15 (30%) eyes with grade 2 CCh; and five (10%) eyes with grade 3 CCh. CCh was located in the inferior bulbar conjunctiva in 45 (90%) eyes, and in the remaining five (10%) CCh was located in the superior bulbar conjunctiva. Ten (33.3%) patients had no symptoms. Dryness, eye pain, redness, blurry vision, tired eye feeling, and epiphora were the symptoms encountered in the remaining twenty (63.6%) patients. Altered tear meniscus was noted in all cases. The mean tear break-up time was 7.6 seconds. The mean Schirmer 1 test score was 7 mm. Pinguecula was found in ten patients.ConclusionDryness, eye pain, redness, blurry vision, and epiphora were the main symptoms in patients with CCh. Dryness, eye pain, and blurry vision were worsened during downgaze and blinking. So CCh should be taken into consideration in the differential diagnosis of chronic ocular irritation and epiphora.

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“…Moreover, TSG-6 amplifies hyaluronan synthesis in murine airway SMCs (32) . A previous study showed that TSG-6 exerts an anti-inflammatory function by counteracting the transcription of MMP-1 and -3 and the activation of MMP-1 in human fibroblasts (33) . In the present study, up-regulation of collagens and MMPs by TSG-6 in VSMCs may be associated with vascular tissue injury, repair, and regeneration with inflammation (34) .…”

Section: Discussionmentioning

confidence: 97%

Atheroprotective Effects of Tumor Necrosis Factor–Stimulated Gene-6

Watanabe

Takahashi

et al. 2016

JACC: Basic to Translational Science

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TSG-6 Controls Transcription and Activation of Matrix Metalloproteinase 1 in Conjunctivochalasis

Abstract: TSG-6 exerts an anti-inflammatory function by counteracting the transcription of MMP-1 and MMP-3 and the activation of MMP-1. Dysfunction of TSG-6 might play a role in the pathogenesis of CCh.

Cited by 17 publications

References 42 publications

PTX3 Controls Activation of Matrix Metalloproteinase 1 and Apoptosis in Conjunctivochalasis Fibroblasts

PTX3 Controls Activation of Matrix Metalloproteinase 1 and Apoptosis in Conjunctivochalasis Fibroblasts

Clinical characteristics of patients with conjunctivochalasis

Atheroprotective Effects of Tumor Necrosis Factor–Stimulated Gene-6

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