SPAK Deficiency Attenuates Chemotherapy-Induced Intestinal Mucositis

IntroductionSte20-related protein proline/alanine-rich kinase (SPAK) affects cell proliferation, differentiation, and transformation, and sodium and chloride transport in the gut. However, its role in gut injury pathogenesis is unclear.ObjectiveWe determined the role of SPAK in chemotherapy-induced...

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Autores principales:	Tien-Yu Huang, Sung-Sen Yang, Ching-Len Liao, Ming-Hong Lin, Hsuan-Hwai Lin, Jung-Chun Lin, Peng-Jen Chen, Yu-Lueng Shih, Wei-Kuo Chang, Tsai-Yuan Hsieh
Formato:	article
Lenguaje:	EN
Publicado:	Frontiers Media S.A. 2021
Materias:	chemotherapy-induced intestinal mucositis gut homeostasis enterocytes tight junctions small intestine 5-fluorouracil Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
Acceso en línea:	https://doaj.org/article/7c8b75489e844c939db758682077c78e
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spelling	oai:doaj.org-article:7c8b75489e844c939db758682077c78e2021-11-30T11:39:43ZSPAK Deficiency Attenuates Chemotherapy-Induced Intestinal Mucositis2234-943X10.3389/fonc.2021.733555https://doaj.org/article/7c8b75489e844c939db758682077c78e2021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fonc.2021.733555/fullhttps://doaj.org/toc/2234-943XIntroductionSte20-related protein proline/alanine-rich kinase (SPAK) affects cell proliferation, differentiation, and transformation, and sodium and chloride transport in the gut. However, its role in gut injury pathogenesis is unclear.ObjectiveWe determined the role of SPAK in chemotherapy-induced intestinal mucositis using in vivo and in vitro models.MethodsUsing SPAK-knockout (KO) mice, we evaluated the severity of intestinal mucositis induced by 5-fluorouracil (5-FU) by assessing body weight loss, histological changes in the intestinal mucosa, length of villi in the small intestine, pro-inflammatory cytokine levels, proliferative indices, and apoptotic indices. We also evaluated changes in gut permeability and tight junction-associated protein expression. Changes in cell permeability, proliferation, and apoptosis were assessed in SPAK siRNA-transfected 5FU-treated IEC-6 cells.Results5-FU-treated SPAK-KO mice exhibited milder intestinal mucositis, reduced pro-inflammatory cytokine expression, increased villus length, good maintenance of proliferative indices of villus cells, decreased apoptotic index of enterocytes, reduced gut permeability, and restoration of tight junction protein expression (vs. 5-FU-treated wild-type mice). Under in vitro conditions, siRNA-mediated SPAK-knockdown in IEC-6 cells decreased cell permeability and maintained homeostasis following 5-FU treatment.ConclusionSPAK deficiency attenuated chemotherapy-induced intestinal mucositis by modulating gut permeability and tight junction-associated protein expression and maintaining gut homeostasis in murine small intestinal tissues following gut injury. The expression of SPAK may influence the pathogenesis of chemotherapy-induced intestinal mucositis.Tien-Yu HuangTien-Yu HuangSung-Sen YangSung-Sen YangSung-Sen YangChing-Len LiaoMing-Hong LinHsuan-Hwai LinJung-Chun LinPeng-Jen ChenYu-Lueng ShihWei-Kuo ChangTsai-Yuan HsiehFrontiers Media S.A.articlechemotherapy-induced intestinal mucositisgut homeostasisenterocytestight junctionssmall intestine5-fluorouracilNeoplasms. Tumors. Oncology. Including cancer and carcinogensRC254-282ENFrontiers in Oncology, Vol 11 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	chemotherapy-induced intestinal mucositis gut homeostasis enterocytes tight junctions small intestine 5-fluorouracil Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
spellingShingle	chemotherapy-induced intestinal mucositis gut homeostasis enterocytes tight junctions small intestine 5-fluorouracil Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 Tien-Yu Huang Tien-Yu Huang Sung-Sen Yang Sung-Sen Yang Sung-Sen Yang Ching-Len Liao Ming-Hong Lin Hsuan-Hwai Lin Jung-Chun Lin Peng-Jen Chen Yu-Lueng Shih Wei-Kuo Chang Tsai-Yuan Hsieh SPAK Deficiency Attenuates Chemotherapy-Induced Intestinal Mucositis
description	IntroductionSte20-related protein proline/alanine-rich kinase (SPAK) affects cell proliferation, differentiation, and transformation, and sodium and chloride transport in the gut. However, its role in gut injury pathogenesis is unclear.ObjectiveWe determined the role of SPAK in chemotherapy-induced intestinal mucositis using in vivo and in vitro models.MethodsUsing SPAK-knockout (KO) mice, we evaluated the severity of intestinal mucositis induced by 5-fluorouracil (5-FU) by assessing body weight loss, histological changes in the intestinal mucosa, length of villi in the small intestine, pro-inflammatory cytokine levels, proliferative indices, and apoptotic indices. We also evaluated changes in gut permeability and tight junction-associated protein expression. Changes in cell permeability, proliferation, and apoptosis were assessed in SPAK siRNA-transfected 5FU-treated IEC-6 cells.Results5-FU-treated SPAK-KO mice exhibited milder intestinal mucositis, reduced pro-inflammatory cytokine expression, increased villus length, good maintenance of proliferative indices of villus cells, decreased apoptotic index of enterocytes, reduced gut permeability, and restoration of tight junction protein expression (vs. 5-FU-treated wild-type mice). Under in vitro conditions, siRNA-mediated SPAK-knockdown in IEC-6 cells decreased cell permeability and maintained homeostasis following 5-FU treatment.ConclusionSPAK deficiency attenuated chemotherapy-induced intestinal mucositis by modulating gut permeability and tight junction-associated protein expression and maintaining gut homeostasis in murine small intestinal tissues following gut injury. The expression of SPAK may influence the pathogenesis of chemotherapy-induced intestinal mucositis.
format	article
author	Tien-Yu Huang Tien-Yu Huang Sung-Sen Yang Sung-Sen Yang Sung-Sen Yang Ching-Len Liao Ming-Hong Lin Hsuan-Hwai Lin Jung-Chun Lin Peng-Jen Chen Yu-Lueng Shih Wei-Kuo Chang Tsai-Yuan Hsieh
author_facet	Tien-Yu Huang Tien-Yu Huang Sung-Sen Yang Sung-Sen Yang Sung-Sen Yang Ching-Len Liao Ming-Hong Lin Hsuan-Hwai Lin Jung-Chun Lin Peng-Jen Chen Yu-Lueng Shih Wei-Kuo Chang Tsai-Yuan Hsieh
author_sort	Tien-Yu Huang
title	SPAK Deficiency Attenuates Chemotherapy-Induced Intestinal Mucositis
title_short	SPAK Deficiency Attenuates Chemotherapy-Induced Intestinal Mucositis
title_full	SPAK Deficiency Attenuates Chemotherapy-Induced Intestinal Mucositis
title_fullStr	SPAK Deficiency Attenuates Chemotherapy-Induced Intestinal Mucositis
title_full_unstemmed	SPAK Deficiency Attenuates Chemotherapy-Induced Intestinal Mucositis
title_sort	spak deficiency attenuates chemotherapy-induced intestinal mucositis
publisher	Frontiers Media S.A.
publishDate	2021
url	https://doaj.org/article/7c8b75489e844c939db758682077c78e
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SPAK Deficiency Attenuates Chemotherapy-Induced Intestinal Mucositis

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