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Type IV collagen ?6 chain is a regulator of keratin 10 in keratinization of oral mucosal epithelium.

ABSTRACT: Keratinized mucosa is of fundamental importance to maintain healthy gingival tissue, and understanding the mechanisms of oral mucosa keratinization is crucial to successfully manage healthy gingiva. Previous studies have shown a strong involvement of the basement membrane in the proliferation and differentiation of epithelial cells. Therefore, first, to identify the keratinized mucosa-specific basement membrane components, immunohistochemical analysis for the six alpha chains of type IV collagen was performed in 8-week-old mice. No difference in the expression pattern of type IV collagen ?1(IV) and ?2(IV) chains was observed in the keratinized and non-keratinized mucosa. Interestingly, however, type IV collagen ?5(IV) and ?6(IV) chains specifically were strongly detected in the keratinized mucosa. To analyze the functional roles of the type IV collagen isoform ?6(IV) in oral mucosa keratinization, we analyzed Col4a6-knockout mice. Epithelial developmental delay and low levels of KRT10 were observed in new-born Col4a6-knockout mice. Additionally, in vitro experiments with loss-of function analysis using human gingival epithelial cells confirmed the important role of ?6(IV) chain in epithelial keratinization. These findings indicate that ?112:?556 (IV) network, which is the only network that includes the ?6(IV) chain, is one regulator of KRT10 expression in keratinization of oral mucosal epithelium.

SUBMITTER: Komori T

PROVIDER: S-EPMC5805778 | biostudies-literature | 2018 Feb

REPOSITORIES: biostudies-literature

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Type IV collagen α6 chain is a regulator of keratin 10 in keratinization of oral mucosal epithelium.

Komori Taishi T Ono Mitsuaki M Hara Emilio Satoshi ES Ueda Junji J Nguyen Ha Thi Thu HTT Nguyen Ha Thi HT Yonezawa Tomoko T Maeba Takahiro T Kimura-Ono Aya A Takarada Takeshi T Momota Ryusuke R Maekawa Kenji K Kuboki Takuo T Oohashi Toshitaka T

Scientific reports 20180208 1

Keratinized mucosa is of fundamental importance to maintain healthy gingival tissue, and understanding the mechanisms of oral mucosa keratinization is crucial to successfully manage healthy gingiva. Previous studies have shown a strong involvement of the basement membrane in the proliferation and differentiation of epithelial cells. Therefore, first, to identify the keratinized mucosa-specific basement membrane components, immunohistochemical analysis for the six alpha chains of type IV collagen ...[more]

PMID: 29422532

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Project description:PurposeTo evaluate the expression patterns of cytokeratin (K) 12, 13, and 19 in normal epithelium of the human ocular surface to determine whether K13 could be used as a marker for conjunctival epithelium.MethodsTotal RNA was isolated from the human conjunctiva and central cornea. Those transcripts that had threefolds or higher expression levels in the conjunctiva than the cornea were identified using microarray technique. Expression levels of three known signature genes and of two conjunctival genes, K13 and K19 were confirmed by using quantitative real-time PCR (qRT-PCR). Protein expression of K12, K13, and K19 was confirmed by immunostaining with specific antibodies on histologic sections of human sclerocornea that contained the conjunctiva, limbus, and cornea and on impression cytology (IC) specimens of the cornea and conjunctiva from normal donors. Double staining of K13/K12 and K19/K12 on histologic sections and IC specimens was performed.ResultsThere were 337 transcripts that were preferentially expressed in the conjunctiva. K13 and K19 were among the top twenty transcripts in the conjunctiva and this preferential expression pattern of K13 and K19 was confirmed by qRT-PCR. Immunohistochemical studies showed that K13 was expressed at the posterior limbal epithelium and conjunctival epithelium but was totally absent in the cornea. K12 was expressed in the corneal and anterior limbal epithelia except for the basal layer and was absent from the conjunctiva. In contrast, K19 was detected in the corneal, limbal and conjunctival epithelia. Immunostaining of the IC specimens showed K12(+) epithelial cells in the corneal region, K13(+) cells in the conjunctival area, and K19(+) cells in the corneal and conjunctival specimens. Expression of K13 and K12 on the ocular surface was mutually exclusive on both the histologic and IC samples using double immunostaining.ConclusionsK13 is more specific to the conjunctival epithelial cells than K19 and potentially could be used as a marker to identify conjunctival epithelial cells in limbal stem cell deficiency.

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Type IV collagen ?6 chain is a regulator of keratin 10 in keratinization of oral mucosal epithelium.

Publications

Type IV collagen α6 chain is a regulator of keratin 10 in keratinization of oral mucosal epithelium.

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