RGD Reference Report - TSG-6 controls transcription and activation of matrix metalloproteinase 1 in conjunctivochalasis. - Rat Genome Database

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TSG-6 controls transcription and activation of matrix metalloproteinase 1 in conjunctivochalasis.

Authors: Guo, P  Zhang, SZ  He, H  Zhu, YT  Tseng, SC 
Citation: Guo P, etal., Invest Ophthalmol Vis Sci. 2012 Mar 15;53(3):1372-80. doi: 10.1167/iovs.11-8738. Print 2012 Mar.
RGD ID: 7777184
Pubmed: PMID:22297496   (View Abstract at PubMed)
PMCID: PMC3339910   (View Article at PubMed Central)
DOI: DOI:10.1167/iovs.11-8738   (Journal Full-text)

PURPOSE: To investigate the role of anti-inflammatory TSG-6 in controlling MMP-1 and MMP-3, which have been shown to be upregulated in conjunctivochalasis (CCh). METHODS: Immunostaining of TSG-6 was compared between normal and CCh conjunctiva and Tenon's capsule. Second cultures of normal and CCh fibroblasts were transfected with or without TSG-6 siRNA and then with or without the addition of TNF-alpha or IL-1beta. Cell lysates and culture media were collected to assess apoptosis with the use of ELISA and the expression of TSG-6, MMP-1, and MMP-3 transcripts and proteins with the use of qRT-PCR and Western blot analysis, respectively. RESULTS: TSG-6 expression was constitutive in the in vivo normal conjunctival epithelium. Significantly more TSG-6-positive cells than normal specimens were noted in CCh subconjunctival tissue and Tenon's capsule. TSG-6 was constitutively expressed intracellularly by both resting normal and CCh fibroblasts but was secreted extracellularly only by resting CCh fibroblasts. Intracellular and extracellular TSG-6 proteins were markedly upregulated by TNF-alpha or IL-1beta in normal and CCh fibroblasts. Active MMP-1 was found in CCh fibroblasts intracellularly and extracellularly, whereas only proMMP-1 was found intracellularly in normal fibroblasts. Knockdown by TSG-6 siRNA upregulated more MMP-1 than MMP-3 transcripts in normal and CCh fibroblasts. TSG-6 siRNA led to extracellular MMP-1 expression by normal fibroblasts such as CCh fibroblasts. This activation of MMP-1 was further enhanced by IL-1beta. Cell apoptosis was higher in CCh fibroblasts and further aggravated by TSG-6 siRNA knockdown. CONCLUSIONS: 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.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
conjunctival disease  IEP 7777184 RGD 
conjunctival disease  ISOTNFAIP6 (Homo sapiens)7777184; 7777184 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Tnfaip6  (TNF alpha induced protein 6)

Genes (Mus musculus)
Tnfaip6  (tumor necrosis factor alpha induced protein 6)

Genes (Homo sapiens)
TNFAIP6  (TNF alpha induced protein 6)


Additional Information