The role of extracellular matrix in the regeneration
1. THE ROLE OF EXTRACELLULAR MATRIX
IN THE REGENERATION
OF SALIVARY GLAND FUNCTION
by
EBEGBONI HANS
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2. Outline
The salivary gland and its function
The Extracellular Matrix and Salivary gland function
Extracellular Matrix and Salivary gland dysfunction
Extracellular Matrix and Salivary gland regeneration
Experimental evidences
Conclusion
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3. The salivary gland and its function
Salivary glands are exocrine glands that are
located in the oral cavity.
The functions of salivary gland is to
produce saliva
store saliva
And release saliva in the mouth when needed
Lin et al., 2018
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Fig 1; location of salivary gland
4. The Extracellular Matrix and Salivary gland function
Extracellular Matrix (ECM) provides tensile
strength for the SG
Lozzo and Schaefer 2015
ECM remodelling is required to allow repetitive
formation of epithelial clefts and end buds
Rozario and DeSimone 2010
ECM play a central role in organizing complex
interactions of the basement membranes,
partnering with other proteins in SG
Chibly et al., 2022
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Fig 2; ECM location in a salivary gland
5. ECM and Salivary gland dysfunction
Salivary Gland dysfunctions can be Autoimmune, Developmental and Physical
Fig 3; Phynotypes of salivary gland dysfunction
chibly et al., 2022; Ren Xu 2016
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6. ECM and Salivary gland dysfunction
Dysregulation of ECM composition, structure, stiffness and abundance contributes to several pathological
conditions, such as fibrosis and invasive cancer.
In humans, the most dramatic change in the SG after IR damage is the replacement of glandular tissue by
excess extracellular matrix deposition resulting in fibrosis that develops weeks to months after treatment.
Alterations in salivary gland such as the extracellular matrix may disrupt communication signals that would
otherwise instruct the gland to regenerate
Increased activity of ECM-degrading proteinases, such as collagenase, alters branching morphogenesis in
salivary gland
The degradation of ECM upon the actions of Matrix metalloproteinases led to the release of soluble damage-
associated molecules resulting in pathogen-mediated inflammation
Feta et al., 2003; Gao et al., 2022
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7. ECM and salivary gland regeneration
ECM are important for facilitating and regulating repair and regeneration of
salivary glands by promoting membrane polarization.
ECM-based scaffolds can be used to culture and differentiate tissue-specific
progenitor cell populations into composite glandular structures
ECM initiates crucial biochemical and biomechanical cues required for tissue
growth in salivary gland
ECM are involved in providing substrate for epithelial cells to move to cover the
damage tissues and re-establish an intact epithelial barrier
Holmberg and Hoffman, 2014
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8. Experimental evidences
Tran and her colleagues (2022), demonstrated that ECM induced in BM-MSCs gotten from
a rat model is capable of trans-differentiating to the SG epithelial cell lineage
This shows that ECM has the ability to in induce regeneration in salivary gland
Fig 4 isolation of BM-MSCs salivary gland like organoid
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7 days 7 days
9. Experimental evidences Cont.
Wang and Gao (2014), also demonstrated that ECM has the ability to induce SG
regeneration, BY taking the SMG-ECM scaffold from a rat with the use of a
decellularization method.
Histological analysis showed acinar-like tissues were regenerated after 14 day culture
Acinar like tissue
SG cells SMG-ECM scalfold SG and ECM scaffold
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Fig 5
14 days
10. Conclusion
The ECM is pivotal in the regeneration and proper
functioning of the SG and should be considered in the
management of SG dysfunctions
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11. Selected References
Sakai T, Larsen M, Yamada KM. Fibronectin requirement in branching
morphogenesis. Nature 423: 876–881, 2003
Lozzo RV, Schaefer L. Proteoglycan form and function: a
comprehensive nomenclature of proteoglycans. Matrix Biol 42: 11–55,
2015
Rozario T, DeSimone DW. The extracellular matrix in development and
morphogenesis: a dynamic view. Dev Biol 341: 126–140, 2010
Walma DA, Yamada KM. The extracellular matrix in development.
Development 147: dev175596, 2020
Chibly, A., Aure, M., Patel, V., & Hoffman, M. P. (2022). SALIVARY
GLAND FUNCTION, DEVELOPMENT, AND REGENERATION. Physiological
Reviews, 102(3), 1495–1552.
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