Downregulation of p38 MAPK Signaling Pathway Ameliorates Tissue-Engineered Corneal Epithelium

Yi Mao; Shangkun Ou; Chengfang Zhu; Sijie Lin; Xiaodong Liu; Minghui Liang; Jingwen Yu; Yiming Wu; Hui He; Rongrong Zong; Zhirong Lin; Zuguo Liu; Wei Li

doi:10.1089/ten.tea.2022.0082

Downregulation of p38 MAPK Signaling Pathway Ameliorates Tissue-Engineered Corneal Epithelium

Yi Mao, Shangkun Ou, Chengfang Zhu, Sijie Lin, Xiaodong Liu, Minghui Liang, Jingwen Yu, Yiming Wu, Hui He, Rongrong Zong, Zhirong Lin, Zuguo Liu, Wei Li^*

^*Corresponding author for this work

Biomedical Sciences

Research output: Contribution to journal › Article › peer-review

Abstract

Tissue-engineered corneal epithelium transplantation is effective treatment for severe limbal stem cell deficiency (LSCD), while epithelial terminal differentiation, tans-differentiation, and insufficient stem cell during construction affect the quality of tissue-engineered corneal epithelium. In this study, we applied SB203580 in the culture medium to downregulate the p38 mitogen-activated protein kinase (MAPK) signaling pathway during construction of tissue-engineered corneal epithelium. With application of SB203580, tissue-engineered corneal epithelium showed enhanced strength and condensed structure. The expression of progenitor cell markers ATP-binding cassette sub-family G member 2, tumor protein p63, keratin 14, and Wnt family member 7A was increased, differentiation markers keratin 12, paired box 6, keratin 10, and keratin 13 and trans-differentiation markers actin alpha 2, smooth muscle and snail family transcriptional repressor 1 was decreased, while cell junction markers claudin 1 and cadherin 1 was increased in the tissue-engineered corneal epithelium. The Wnt/catenin beta 1 signaling pathway was upregulated in the epithelium after p38 MAPK inhibition. Transplantation of tissue-engineered corneal epithelium treated with SB203580 to rabbit LSCD model showed faster wound healing and improved epithelial quality. We conclude that downregulation of p38 MAPK signaling pathway helps maintain the stemness and prevent terminal differentiation and abnormal differentiation of corneal epithelial cells during epithelium construction process, and thus can improve the quality of tissue-engineered corneal epithelium.

Original language	English
Pages (from-to)	977-989
Number of pages	13
Journal	Tissue Engineering - Part A
Volume	28
Issue number	23-24
Early online date	6 Sept 2022
DOIs	https://doi.org/10.1089/ten.tea.2022.0082
Publication status	Published - 13 Dec 2022

Bibliographical note

Funding Information:
This study is supported, in part, by the National Key R&D Program of China (2018YFA0107301 [to W.L.]), the National Natural Science Foundation of China (NSFC; No. 81870625 [to R.Z.], No. 81970773 [to W.L.], No. 82101084 [to S.O.]), and the China Postdoctoral Science Foundation (2021M69898 [to S.O.]). The funders have no role in the study design, data collection and analysis, decision on publishing, or preparation of the article.

Keywords

p38 MAPK
tissue-engineered corneal epithelium
limbal stem cell deficiency
limbal stem cell

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10.1089/ten.tea.2022.0082

Cite this

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title = "Downregulation of p38 MAPK Signaling Pathway Ameliorates Tissue-Engineered Corneal Epithelium",

abstract = "Tissue-engineered corneal epithelium transplantation is effective treatment for severe limbal stem cell deficiency (LSCD), while epithelial terminal differentiation, tans-differentiation, and insufficient stem cell during construction affect the quality of tissue-engineered corneal epithelium. In this study, we applied SB203580 in the culture medium to downregulate the p38 mitogen-activated protein kinase (MAPK) signaling pathway during construction of tissue-engineered corneal epithelium. With application of SB203580, tissue-engineered corneal epithelium showed enhanced strength and condensed structure. The expression of progenitor cell markers ATP-binding cassette sub-family G member 2, tumor protein p63, keratin 14, and Wnt family member 7A was increased, differentiation markers keratin 12, paired box 6, keratin 10, and keratin 13 and trans-differentiation markers actin alpha 2, smooth muscle and snail family transcriptional repressor 1 was decreased, while cell junction markers claudin 1 and cadherin 1 was increased in the tissue-engineered corneal epithelium. The Wnt/catenin beta 1 signaling pathway was upregulated in the epithelium after p38 MAPK inhibition. Transplantation of tissue-engineered corneal epithelium treated with SB203580 to rabbit LSCD model showed faster wound healing and improved epithelial quality. We conclude that downregulation of p38 MAPK signaling pathway helps maintain the stemness and prevent terminal differentiation and abnormal differentiation of corneal epithelial cells during epithelium construction process, and thus can improve the quality of tissue-engineered corneal epithelium.",

keywords = "p38 MAPK, tissue-engineered corneal epithelium, limbal stem cell deficiency, limbal stem cell",

author = "Yi Mao and Shangkun Ou and Chengfang Zhu and Sijie Lin and Xiaodong Liu and Minghui Liang and Jingwen Yu and Yiming Wu and Hui He and Rongrong Zong and Zhirong Lin and Zuguo Liu and Wei Li",

note = "Funding Information: This study is supported, in part, by the National Key R&D Program of China (2018YFA0107301 [to W.L.]), the National Natural Science Foundation of China (NSFC; No. 81870625 [to R.Z.], No. 81970773 [to W.L.], No. 82101084 [to S.O.]), and the China Postdoctoral Science Foundation (2021M69898 [to S.O.]). The funders have no role in the study design, data collection and analysis, decision on publishing, or preparation of the article.",

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doi = "10.1089/ten.tea.2022.0082",

language = "English",

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journal = "Tissue Engineering - Part A",

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T1 - Downregulation of p38 MAPK Signaling Pathway Ameliorates Tissue-Engineered Corneal Epithelium

AU - Mao, Yi

AU - Ou, Shangkun

AU - Zhu, Chengfang

AU - Lin, Sijie

AU - Liu, Xiaodong

AU - Liang, Minghui

AU - Yu, Jingwen

AU - Wu, Yiming

AU - He, Hui

AU - Zong, Rongrong

AU - Lin, Zhirong

AU - Liu, Zuguo

AU - Li, Wei

N1 - Funding Information: This study is supported, in part, by the National Key R&D Program of China (2018YFA0107301 [to W.L.]), the National Natural Science Foundation of China (NSFC; No. 81870625 [to R.Z.], No. 81970773 [to W.L.], No. 82101084 [to S.O.]), and the China Postdoctoral Science Foundation (2021M69898 [to S.O.]). The funders have no role in the study design, data collection and analysis, decision on publishing, or preparation of the article.

PY - 2022/12/13

Y1 - 2022/12/13

N2 - Tissue-engineered corneal epithelium transplantation is effective treatment for severe limbal stem cell deficiency (LSCD), while epithelial terminal differentiation, tans-differentiation, and insufficient stem cell during construction affect the quality of tissue-engineered corneal epithelium. In this study, we applied SB203580 in the culture medium to downregulate the p38 mitogen-activated protein kinase (MAPK) signaling pathway during construction of tissue-engineered corneal epithelium. With application of SB203580, tissue-engineered corneal epithelium showed enhanced strength and condensed structure. The expression of progenitor cell markers ATP-binding cassette sub-family G member 2, tumor protein p63, keratin 14, and Wnt family member 7A was increased, differentiation markers keratin 12, paired box 6, keratin 10, and keratin 13 and trans-differentiation markers actin alpha 2, smooth muscle and snail family transcriptional repressor 1 was decreased, while cell junction markers claudin 1 and cadherin 1 was increased in the tissue-engineered corneal epithelium. The Wnt/catenin beta 1 signaling pathway was upregulated in the epithelium after p38 MAPK inhibition. Transplantation of tissue-engineered corneal epithelium treated with SB203580 to rabbit LSCD model showed faster wound healing and improved epithelial quality. We conclude that downregulation of p38 MAPK signaling pathway helps maintain the stemness and prevent terminal differentiation and abnormal differentiation of corneal epithelial cells during epithelium construction process, and thus can improve the quality of tissue-engineered corneal epithelium.

AB - Tissue-engineered corneal epithelium transplantation is effective treatment for severe limbal stem cell deficiency (LSCD), while epithelial terminal differentiation, tans-differentiation, and insufficient stem cell during construction affect the quality of tissue-engineered corneal epithelium. In this study, we applied SB203580 in the culture medium to downregulate the p38 mitogen-activated protein kinase (MAPK) signaling pathway during construction of tissue-engineered corneal epithelium. With application of SB203580, tissue-engineered corneal epithelium showed enhanced strength and condensed structure. The expression of progenitor cell markers ATP-binding cassette sub-family G member 2, tumor protein p63, keratin 14, and Wnt family member 7A was increased, differentiation markers keratin 12, paired box 6, keratin 10, and keratin 13 and trans-differentiation markers actin alpha 2, smooth muscle and snail family transcriptional repressor 1 was decreased, while cell junction markers claudin 1 and cadherin 1 was increased in the tissue-engineered corneal epithelium. The Wnt/catenin beta 1 signaling pathway was upregulated in the epithelium after p38 MAPK inhibition. Transplantation of tissue-engineered corneal epithelium treated with SB203580 to rabbit LSCD model showed faster wound healing and improved epithelial quality. We conclude that downregulation of p38 MAPK signaling pathway helps maintain the stemness and prevent terminal differentiation and abnormal differentiation of corneal epithelial cells during epithelium construction process, and thus can improve the quality of tissue-engineered corneal epithelium.

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DO - 10.1089/ten.tea.2022.0082

M3 - Article

SN - 1937-3341

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JO - Tissue Engineering - Part A

JF - Tissue Engineering - Part A

IS - 23-24

ER -

Downregulation of p38 MAPK Signaling Pathway Ameliorates Tissue-Engineered Corneal Epithelium

Abstract

Bibliographical note

Keywords

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