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invasion.
101
We found that fibroblasts from bleomycin-treated
b
-arrestin-
deficient mice and human IPF fibroblasts with
b
-arrestin 2 knockdown
failed to invade extracellular matrix.
131
Furthermore, we showed that loss
of
b
-arrestin 1 or
b
-arrestin 2 in primary lung fibroblasts resulted in altered
expression of genes involved in matrix production, basement membrane
degradation, and cell adhesion.
131
Therefore, this study suggests that
inhibiting
b
-arrestin expression in lung fibroblasts would be a potential ther-
apy for IPF and other types of pulmonary fibrosis.
b
-Arrestin 1 expression is increased in T cells from primary biliary cir-
rhosis patients. There is also a positive correlation between the levels of
b
-arrestin 1 mRNA in peripheral blood mononuclear cells and progression
of cirrhosis.
59
b
-Arrestin 1 was overexpressed in autoreactive T cells from
cirrhotic patients and augmented cell proliferation, increased interferon
release, and regulated autoimmune-related gene expression.
59
The study
suggests that
b
-arrestin 1 overexpression contributes to the pathogenesis
of primary biliary cirrhosis. Angiotensin II binds the angiotensin II type
1A receptor to mediate inflammatory and fibrotic responses.
83
b
-Arrestins
regulate desensitization and sequestration of AGTR1.
85,149
In cirrhosis,
impaired vascular reactivity leads to vasodilation and contributes to portal
hypertension. Vascular hyporesponsiveness to angiotensin II in CCL4-
treated rats is due to enhanced interaction of the AGTR1 with
b
-arrestin
2 and alterations in receptor function.
150
Silencing
b
-arrestins might be a
therapeutic strategy for cirrhosis.
6.3. Arthritis
Rheumatoid arthritis is an autoimmune disease characterized by joint
inflammation and destruction. GPCRs, such as chemokine receptors,
G-protein-coupled receptor kinases, and
b
-arrestin1 and 2 are involved
in the pathogenesis of rheumatoid arthritis. Reduction in GRK activity with
a decreased level of GRK-2 and GRK-6 protein expression was found in
patients with rheumatoid arthritis, while
b
-arrestin-1 expression was
unchanged between rheumatoid arthritis patients and controls.
151
In a rat
adjuvant arthritis model, the expression of
b
-arrestin 1 in splenocytes was
increased at the most severe period of the disease.
152
Using collagen-induced
arthritis and human TNF
a
transgenic mouse models, another group dem-
onstrated that expression of
b
-arrestin 1 and 2 was elevated in joint tissue.
153
Furthermore,
b
-arrestins differentially regulated inflammatory cytokine
production by fibroblast-like synoviocytes, in which
b
-arrestin 1 increased
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