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Gene & Protein in Disease Exosomes connect periodontitis and systemic diseases

5.2. Periodontitis increases the incidence of chronic loss of neurons [9,117] . Ide et al. assessed the cognition of 60
kidney disease (CKD) people with mild-to-moderate AD and took blood samples
As a progressive pathological condition, renal fibrosis is for screening markers of inflammation and found that the
the final outcome of a variety of CKDs [103,104] . Renal fibrosis presence of periodontitis was associated with a 6-fold
is characterized by excessive accumulation of fibroblasts increase in the rate of cognitive decline as assessed. This
and cell matrix, which eventually leads to end-stage renal indicates that periodontitis is associated with worsened
disease [105,106] . On the one hand, various pathogenic factors cognitive decline in AD, which may be mediated through
can stimulate the intrinsic cells of kidney and promote the effects on systemic inflammation [118] .
proliferation of fibroblasts leading to fibrosis [105] , and on the Exosomes are one of the multiple cellular mechanisms
other hand, accumulated protein can increase glomerular that may link amyloid and tau secretion to both toxicity
protein filtration, which contributes to collagen deposition and neurofibrillary lesion spreading in AD [119,120] . In the
and accumulation, resulting in the gradual hardening of process of the onset of AD, neurons and neuroglial cells
renal parenchyma, the formation of scar, and finally the can release exosomes into the extracellular space or
complete loss of organ functions [107] . The exact pathogenesis transport them to the neighboring cells through blood,
of CKD influenced by periodontitis is currently unclear, and then exosomes can fuse with the membrane and
but it has been reported that the prevalence of chronic release contents, especially miRNAs, into the intracellular
periodontitis would lead to an increase incidence of CKD. plasma to activate TLRs [121] . TLR7-9 activates the myeloid
TGF-β is not only an important cytokine that promotes the differentiation factors (MyD88) and then activates nuclear
development of periodontitis [108] , but also a primary factor factors and transcription factors activator protein-1,
that drives fibrosis in most forms of CKD [109,110] . Chen et leading to neuroinflammation and neuronal death [122] .
al. found that periodontitis caused the downregulation Zheng et al. isolated exosomes from peripheral plasma
of matrix MMP2 and upregulation of tissue inhibitors of and injected them into the hippocampus of an AD mouse
metalloproteinases-1 and TGF-β1 at transcriptional and model, and found that exosomes can diffuse throughout
translational levels by comparing with normal mice; this the brain and clustered around the Aβ plaques, which
is a possible mechanism by which periodontitis aggravates indicates that exosomes may contribute to the spread of
kidney damage [111] . Borges et al. used kidney injury as a Aβ [123] .
model system and demonstrated that injured ECs produce
an increased number of exosomes to activate fibroblasts, 5.4. Periodontitis promotes platelet aggregation
which depends on the exosomes delivering TGF-β1 and cerebral arteriosclerosis which lead to stroke
mRNA [112] . In addition, Sonoda et al. used the rat kidney Stroke is a rapidly progressive ischemic or hemorrhagic
ischemia-reperfusion injury as an acute kidney injury encephalopathy, which can be divided into ischemic stroke
model, and found that miR-16, miR-24, and miR-200c (IS) and hemorrhagic stroke. Hemorrhagic stroke refers
in urine exosomes were increased at the injury stage, and to non-traumatic cerebral parenchymal hemorrhage, also
miR-9a, miR-141, miR-200a, miR-200c, and miR-429 were known as cerebral hemorrhage, mainly occurs in patients
upregulated in the early recovery stage, indicating that with hypertension and cerebral arteriosclerosis [124] . IS is
these miRNAs are related to renal fibrosis [113] .
mainly caused by thromboembolism of the great arteries
5.3. Periodontal pathogens lead to the loss of supplying blood to brain, which leads to necrosis of
neurons and induce AD brain tissue [125] . Periodontitis is associated with stroke.
Sen et al. found that the risk of thrombotic stroke in
AD is a neurodegenerative disorder characterized patients with periodontitis is twice the risk in healthy
by gradual cognitive decline and memory loss, even individuals [126] . Periodontitis is associated with elevated
intellectual loss, or death in some severe cases [114] . AD levels of C-reactive protein, fibrinogen, and cytokines,
is characterized by the presence of insoluble plaques and these inflammatory factors can invade vascular
and tangles composed of Aβ and hyper-phosphorylated endothelial cells, thereby promoting platelet aggregation
tau (p-tau), respectively [115] . At present, more and more and atherosclerotic diseases as well as inducing formation
evidence has shown that inflammation plays a key role in [127,128]
the pathophysiological process of AD, and the relationship of foam cells . This suggests that periodontitis may
between periodontitis and AD has also been confirmed by cause cerebral arteriosclerosis and endothelial cell damage,
which eventually lead to stroke.
relevant studies [116] . Periodontal pathogens can induce the
mutual activation of microglia and inflammatory factors A growing line of evidence demonstrated that exosomes
directly or indirectly, as well as the accumulation of amyloid participate in the development of stroke. Some researchers
Aβ in brain, and eventually lead to a vicious cycle and the extracted circulating exosomes from the blood of patients

Volume 1 Issue 2 (2022) 8 https://doi.org/10.36922/gpd.v1i2.99