6th Annual Symposium
Physics of Cancer
Leipzig, Germany
September 7-9, 2015
Invited Talk
Breaking Barriers: Role of Integrins in Epithelial Homeostasis and Sterile Inflammation
Srikala Raghavan
Center for Inflammation and Tissue Homeostasis, Institute for Stem Cell Biology and Regenerative Medicine (inStem), Bangalore, India
Contact:  | Website
Integrins are heterodimeric trans-membrane receptors that connect the cellular
cytoskeleton to the extracellular matrix and play a vital role in cellular processes such
as proliferation, differentiation, migration and adhesion. We previously reported the
generation/characterization of the conditional knockout of integrin β1 in murine skin
epidermis. These mice displayed a marked failure in the organization of the epithelial
basement membrane (BM) that resulted in the loss of adhesion between the
epidermis and the underlying dermis, thereby leading to neonatal lethality.
Additionally integrin beta1 KO keratinocytes display defects in focal adhesion
turnover, and establisment of normal cell-cell junctions resulting in severely impaired
directed cell migration.

Further characterization of the β1 KO skin unexpectedly revealed a strong
inflammatory and wound response, which is associated with the recruitment of
immune cells from both the innate and adaptive immune system. Of particular
importance is the fact that this immune response is during embryonic development,
i.e., in the presence of an intact barrier, and at a time when there are no extrinsic
wounds or skin microbiome that may facilitate this process. Additionally if the sterile
stimulus is not resolved, it can lead to chronic inflammation and tissue damage. We
demonstrate that administration of anti-inflammatory drugs can largely rescue the
ECM organization of the β1 KO mice. Therefore, we propose that the epidermisspecific
β1-integrin KO provides us with a unique model system to address the
molecular basis of sterile inflammation, which remains poorly understood. Moreover
our KO model could serve as a screening platform for drugs that may dampen this
effect and thus work as future therapeutics for chronic inflammatory conditions of the
skin.
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