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LGI 3 promotes human keratinocyte differentiation via the Akt pathway
Author(s) -
Kim In Wook,
Jeong HyoSoon,
Kwon Nyoun Soo,
Baek Kwang Jin,
Yun HyeYoung,
Kim DongSeok
Publication year - 2018
Publication title -
experimental dermatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.108
H-Index - 96
eISSN - 1600-0625
pISSN - 0906-6705
DOI - 10.1111/exd.13766
Subject(s) - hacat , involucrin , keratinocyte , cellular differentiation , protein kinase a , microbiology and biotechnology , biology , signal transduction , kinase , protein kinase b , cell culture , biochemistry , genetics , gene
Leucine‐rich repeat LGI family member 3 ( LGI 3), a member of the LGI family, is a secreted protein that is expressed not only in the brain and adipose tissues, but also in various skin cells. We previously reported that LGI 3 was secreted after exposure to ultraviolet B and promoted the migration of HaCaT human keratinocytes. In the present study, we investigated whether LGI 3 influences the differentiation of keratinocytes. The results show that the expression of involucrin, a keratinocyte differentiation marker, was reduced in tissue from LGI 3‐knockout mice. Those results indicate that LGI 3 plays an important role in keratinocyte differentiation. Therefore, we treated HaCaT cells with LGI 3 to examine its effect on keratinocyte differentiation. Protein levels of various differentiation markers were enhanced by treatment with LGI 3. Furthermore, expression of differentiation markers was inhibited when keratinocytes were transfected with an si RNA for LGI 3. LGI 3 strongly activated Akt, whereas it had no apparent effect on extracellular signal‐regulated kinase, p38 mitogen‐activated protein kinase, or the c‐Jun N‐terminal kinase. A specific inhibitor of phosphoinositide 3‐kinase, LY 294002, reduced LGI 3‐induced expression of differentiation markers in HaCaT cells. Taken together, these results suggest that LGI 3 promotes keratinocyte differentiation and could be used as a therapeutic agent to recover skin barrier function in epidermal barrier disruption.