Evidence mapPaperPMID 41299222Full record

ArticleCellular & molecular biology letters2025

Loss of alpha-kinase 1 contributes to the formation of congenital cataracts in mice.

Hui-Shan Wang, Yu-Xin Yang, Shang-Shang Duan, Fang-Yi Long, Ting Wu, Nai-Hong Yan, Xiao-Hong Li, Jun-Rong Du

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Article in Cellular & molecular biology letters, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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1 · What the graph read from it

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5 · Who and what money

Authors and funding

8 authors.

Hui-Shan Wang *West China School of Pharmacy, West China School of Public Health, Research Laboratory of Ophthalmology, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan, China.
Yu-Xin Yang *West China School of Pharmacy, West China School of Public Health, Research Laboratory of Ophthalmology, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan, China.
Shang-Shang Duan *West China School of Pharmacy, West China School of Public Health, Research Laboratory of Ophthalmology, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan, China.
Fang-Yi LongLaboratory Medicine Center, Sichuan Provincial Maternity and Child Health Care Hospital, Chengdu, 610032, Sichuan, China.
Ting WuWest China School of Pharmacy, West China School of Public Health, Research Laboratory of Ophthalmology, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan, China.
Nai-Hong YanWest China School of Pharmacy, West China School of Public Health, Research Laboratory of Ophthalmology, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan, China.
Xiao-Hong LiWest China School of Pharmacy, West China School of Public Health, Research Laboratory of Ophthalmology, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan, China. li_xiaohong@scu.edu.cn.ORCID http://orcid.org/0009-0000-6791-5932
Jun-Rong DuWest China School of Pharmacy, West China School of Public Health, Research Laboratory of Ophthalmology, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan, China. dujunrong@scu.edu.cn.

Funding

Aier Eye-Sichuan University Research Foundation 23JZH046
6 · The paper itself

Abstract

backgroundAlpha-kinase 1 (ALPK1), a cytosolic receptor involved in innate immune activation, promotes apical trafficking in epithelial cells. While its role in autoinflammatory disorders is known, its function in epithelial homeostasis remains unexplored. This study investigates ALPK1’s role in murine lens development and its pathological relevance to congenital cataracts (CCs).

methodsWe utilized ALPK1-deficient (ALPK1−/−) C57BL/6 mice and primary lens epithelial cells (LECs) with ALPK1 knockout (via lentiviral sgRNA) to analyze lens histo-morphological alterations and cellular and molecular pathologies, including apical protein transport and localization, endoplasmic reticulum (ER) stress, apoptosis, and LEC differentiation.

resultsWe observed strong ALPK1 immunoreactivity in the LECs of C57BL/6 mice. ALPK1−/− mice developed CCs with combined Y-suture and cortical opacities, disrupted lens cell architecture, and vacuolar degeneration. Molecular dysregulation included reduced phosphorylation of myosin Ia, mislocalization of zonula occludens-1 (ZO-1) from apical tight junctions to cytoplasmic aggregates, upregulation of the endoplasmic reticulum (ER) stress marker C/EBP-homologous protein (CHOP), increased apoptosis (evidenced by TUNEL-positive cells), and disorganized interlocking patterns in lens fiber cells. Lentiviral ALPK1 re-expression in ALPK1−/− mice significantly restored lens transparency and ZO-1 apical localization, reduced CHOP expression, and suppressed apoptosis.

conclusionsThis study first demonstrates that ALPK1 is critical for maintaining LEC homeostasis by regulating myosin Ia phosphorylation-dependent apical trafficking and tight junction integrity. ALPK1 deficiency disrupts these processes, leading to loss of apical polarity, ER stress-induced apoptosis, and ultimately CC formation.

Indexed as

CataractAnimalsApoptosisEndoplasmic Reticulum StressEpithelial CellsLens, CrystallineMiceMice, Inbred C57BLMice, KnockoutTranscription Factor CHOPZonula Occludens-1 ProteinTranscription Factor CHOPZonula Occludens-1 ProteinALPK1Apical transportCongenital cataractsLens epithelial cellsMyosin Ia

Identifiers

PMID41299222
PMCPMC12765290

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.