Enhanced degradation of proteins of the basal lamina and stroma by matrix metalloproteinases from the salivary glands of Sjögren's syndrome patients: Correlation with reduced structural integrity of acini and ducts

Goicovich, Eduardo; Molina, Claudio; Pérez, Paola; Aguilera, Sergio; Fernández, Juan; Olea, Nicolás; Alliende, Cecilia; Leyton, Cecilia; Romo, Rafael; Leyton, Lisette; González, María-Julieta

doi:10.1002/art.11178

Cited by 86 publications

(91 citation statements)

References 56 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Relatively weak type IV collagen ␣5 and ␣6 chain expression in diseased glands may compromise this quality in SS. However, this structural abnormality may be secondary to diminished salivary flow (disuse atrophy) and/or increased local synthesis of matrix metalloproteinases that allows degradation of type IV collagen in the basement membrane (22,(24)(25)(26)(27).…”

Section: Discussionmentioning

confidence: 99%

Abnormal basement membrane type IV collagen α‐chain composition in labial salivary glands in Sjögren's syndrome

Poduval¹,

Sillat²,

Virtanen³

et al. 2009

Arthritis & Rheumatism

View full text Add to dashboard Cite

Objective. Sjögren's syndrome (SS) is characterized by atrophy and malfunction of the acinar cells. The aim of this study was to investigate whether type IV collagen ␣-chain composition of acinar cell compartments could be abnormal in diseased glands.Methods. Messenger RNA (mRNA) from human submandibular gland (HSG) cells, cultured with or without growth factor-depleted Matrigel, was analyzed using quantitative reverse transcription-polymerase chain reaction (RT-PCR). Labial salivary glands were analyzed using quantitative RT-PCR and immunohistochemistry.Results. HSG cells of both the ductal and acinar phenotypes synthesized all ␣-chain mRNA, in particular those of the ␣1 and ␣2 chains. Labial salivary glands (LSGs) contained ␣1/2 chains but also contained mRNA of all the other ␣-chains, although the mRNA copy numbers for the ␣3 and ␣4 chains were low, and the corresponding proteins were absent. Type IV collagen ␣1/2-chains were observed in all tubuloalveolar basement membranes. In healthy glands, ␣5 and ␣6 chains were continuous around ducts but discontinuous around acini. In SS glands, these chains were absent or patchy around the ducts and absent around the acini.Conclusion. Ductal and acinar epithelial cells are able to locally produce mRNA for all 6 different ␣-chains. Type IV collagen ␣1/2-chains seem to form the backbone in the tubuloalveolar basement membrane in salivary glands. Type IV collagen ␣3 and ␣4 chain mRNA were found in cultured salivary epithelial cells and LSG explants but were not translated to the corresponding ␣-chains in LSGs. Both ␣5 and ␣6 mRNA were observed in salivary epithelial cells and glands. In healthy glands, immunolabeling always disclosed corresponding ␣-chains around ducts, but their synthesis and/or degradation seemed to be locally regulated around acinar cells.

show abstract

Section: Discussionmentioning

confidence: 99%

Abnormal basement membrane type IV collagen α‐chain composition in labial salivary glands in Sjögren's syndrome

Poduval¹,

Sillat²,

Virtanen³

et al. 2009

Arthritis & Rheumatism

View full text Add to dashboard Cite

show abstract

“…Desde el punto de vista patogénico, se ha valorado la presencia de una enzima de la matriz extracelular, MMP-9, observada en la membrana basal de los acinos glandulares de los SS primarios 20 . En el HAM/TSP el aumento de enzimas de la matriz extracelular es un fenómeno que no sólo puede dar cuenta del daño glandular, sino que también del daño neurológico 21 .…”

Section: N V E S T I G a C I ó Nunclassified

“…En el HAM/TSP el aumento de enzimas de la matriz extracelular es un fenómeno que no sólo puede dar cuenta del daño glandular, sino que también del daño neurológico 21 . La sobreexpresión de MMP-2, MMP-9 y MMP-3 en el líquido cefalorraquídeo de estos pacientes, así como el aumento de los inhibidores naturales como TIM-1-TIM-2 y TIM-3 21 , son concordantes con la expresión de MMP-9 en las glándulas salivares de los HAM/TSP, así como de la posible intervención de esta enzima en las alteraciones estructurales y funcionales 20,22 .…”

Section: N V E S T I G a C I ó Nunclassified

Proteína Tax (HTLV-I), probable factor patogénico y marcador del síndrome sicca que se asocia a HAM/TSP

Ramı́rez

2005

Rev. méd. Chile

View full text Add to dashboard Cite

show abstract

“…Severe alterations in acinar cells and the extracellular matrix (ECM) are recurrent observations in the labial salivary glands (LSGs) of patients with primary Sjögren's syndrome (SS) (1)(2)(3)(4). LSG epithelial cells are linked to the basal lamina (BL) through several transmembrane protein complexes that have important functions in adhesion and cell signaling (5).…”

mentioning

confidence: 99%

“…In patients with SS, increased proteolysis of nidogens and type I and type III collagens is the consequence of an imbalance of matrix metalloproteinase activity and tissue inhibitors of matrix metalloproteinases (TIMPs) (1,2,7). In addition, LSG samples from patients with SS display reduced immunodetection of laminins 111 and 211, which is paralleled by an increase in laminin 411 at locations distant from inflammatory foci (3).…”

mentioning

confidence: 99%

Alterations in type I hemidesmosome components suggestive of epigenetic control in the salivary glands of patients with Sjögren's syndrome

González

Aguilera

Alliende

et al. 2011

Arthritis & Rheumatism

Self Cite

View full text Add to dashboard Cite

Objective. Acinar cells in the salivary glands of patients with Sjögren's syndrome (SS) display severe alterations in anchorage to the basal lamina. Bioinformatics analysis of the BP230 gene sequence has revealed the presence of CpG islands that might be involved in epigenetic control of gene expression, and methylation of the BP230 promotor region may be implicated as an epigenetic control mechanism in salivary gland damage. Thus, the present study was undertaken to evaluate the protein BP230, as well as proteins BP180, ␣6␤4 integrin, and cytokeratin-18, for their expression levels, localization, and ability to form hemidesmosome adhesion complexes.Methods. Eighteen patients with primary SS and 14 healthy control subjects were studied. Levels of messenger RNA (mRNA) and protein were measured by reverse transcription-polymerase chain reaction and Western blotting, respectively. BP230 methylation was determined by methylation-sensitive polymerase chain reaction. Protein complexes were analyzed by immunoprecipitation and assessed for localization by immunofluorescence.Results. In patients with SS as compared with controls, BP230 mRNA levels were decreased while protein levels were increased, and the gene promotor region was hypermethylated. Augmented proteolysis of BP180 was detected, since levels of linear IgA disease fragment 1 were increased. The complex-forming ability of BP230, BP180, ␣6␤4 integrin, and cytokeratin-18 was maintained in patients with SS, in contrast to that in controls. BP230 and BP180 colocalized at the basal membrane of acinar cells, and cleavage of BP180 coincided with a loss of colocalization.Conclusion. The decrease in BP230 mRNA levels may be explained by gene hypermethylation. We postulate that local epigenetic modifications of BP230 are produced in response to factors present in the damaged salivary glands of patients with SS. Additionally, the paradoxical increase in BP230 protein levels and the formation of both normal and altered adhesion complexes may help avoid cell death induced by the loss of anchorage.Severe alterations in acinar cells and the extracellular matrix (ECM) are recurrent observations in the labial salivary glands (LSGs) of patients with primary Sjögren's syndrome (SS) (1-4). LSG epithelial cells are linked to the basal lamina (BL) through several transmembrane protein complexes that have important functions in adhesion and cell signaling (5). These adhesion complexes include ␣6␤1 and ␣6␤4 integrins as a central

show abstract

Enhanced degradation of proteins of the basal lamina and stroma by matrix metalloproteinases from the salivary glands of Sjögren's syndrome patients: Correlation with reduced structural integrity of acini and ducts

Cited by 86 publications

References 56 publications

Abnormal basement membrane type IV collagen α‐chain composition in labial salivary glands in Sjögren's syndrome

Abnormal basement membrane type IV collagen α‐chain composition in labial salivary glands in Sjögren's syndrome

Proteína Tax (HTLV-I), probable factor patogénico y marcador del síndrome sicca que se asocia a HAM/TSP

Alterations in type I hemidesmosome components suggestive of epigenetic control in the salivary glands of patients with Sjögren's syndrome

Contact Info

Product

Resources

About