Evidence map›Paper›PMID 42012715›Full record

ArticleMolecular biology reports2026

S100A4 expression in the enteric nerve system of young and aged rats.

Fan Xiaoyi, Han Yiman, Xia Tianhao, Huang Kesheng, Xiang Zhenghua, Yuan Hongbin

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Article in Molecular biology reports, 2026. 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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6 authors.

Fan Xiaoyi *Jiangsu Province Key Laboratory of Anesthesiology, Jiangsu Province Key Laboratory of Anesthesia and Analgesia Application Technology, NMPA Key Laboratory for Research and Evaluation of Narcotic and Psychotropic Drugs, Xuzhou Medical University, 209 Tongshan Rd, Xuzhou, 221004, Jiangsu, China.
Han Yiman *Jiangsu Province Key Laboratory of Anesthesiology, Jiangsu Province Key Laboratory of Anesthesia and Analgesia Application Technology, NMPA Key Laboratory for Research and Evaluation of Narcotic and Psychotropic Drugs, Xuzhou Medical University, 209 Tongshan Rd, Xuzhou, 221004, Jiangsu, China.
Xia Tianhao *Jiangsu Province Key Laboratory of Anesthesiology, Jiangsu Province Key Laboratory of Anesthesia and Analgesia Application Technology, NMPA Key Laboratory for Research and Evaluation of Narcotic and Psychotropic Drugs, Xuzhou Medical University, 209 Tongshan Rd, Xuzhou, 221004, Jiangsu, China.
Huang KeshengJiangsu Province Key Laboratory of Anesthesiology, Jiangsu Province Key Laboratory of Anesthesia and Analgesia Application Technology, NMPA Key Laboratory for Research and Evaluation of Narcotic and Psychotropic Drugs, Xuzhou Medical University, 209 Tongshan Rd, Xuzhou, 221004, Jiangsu, China.
Xiang ZhenghuaDepartment of Neurobiology, MOE Key Laboratory of Molecular Neurobiology, Ministry of Education, Second Military Medical University, Shanghai, 200433, PR China. xiang-zhenghua@163.com.
Yuan HongbinJiangsu Province Key Laboratory of Anesthesiology, Jiangsu Province Key Laboratory of Anesthesia and Analgesia Application Technology, NMPA Key Laboratory for Research and Evaluation of Narcotic and Psychotropic Drugs, Xuzhou Medical University, 209 Tongshan Rd, Xuzhou, 221004, Jiangsu, China. jfjczyy@aliyun.com.

Funding

the National Natural Science Foundation of the People's Republic of China 81971046
6 · The paper itself

Abstract

background​ The S100 protein family constitutes a group of calcium-signaling proteins involved in numerous vital physiological and pathological functions. The enteric nervous system, often termed the second brain, regulates the maintenance of gastrointestinal motility, secretion, and immune functions. S100A4 is one member of this extensive family. To date, no reports exist concerning the distribution, cellular localization, or functional role of S100A4 within the gastrointestinal tract.

methods​ The double or triple labeling immunofluorescence technique was employed to investigate the localization and cytochemical characteristics of S100A4-positive neurons in the enteric nervous system. A semi-quantitative analysis was conducted on the changes in the number of S100A4 neurons in the gastrointestinal system of young and aged rats. Colchicine was intraperitoneally injected into aged rats to optimize the visualization of S100A4-positive neurons in their gastrointestinal system. The expression of S100A4 in the gastrointestinal tissues of young, aged, and colchicine-treated aged rats was studied using Western blotting and quantitative real-time reverse transcription PCR techniques.

results​ S100A4 was widely localized in neurons of the enteric nervous system (ENS). Specifically, all S100A4-immunoreactive cells in the myenteric and submucosal ganglia showed co-localization with HuD and calretinin. Partial co-localization was observed with choline acetyltransferase (CHAT) and calbindin, while only a minimal fraction of S100A4-positive cells co-existed with NF200-positive neurons. Notably, aging resulted in a significant reduction in S100A4-positive cell numbers within the ENS. However, the staining intensity of S100A4 markedly increased in nerve bundles and terminals. In contrast, the population of HuD-positive cells remained stable between young and aged rats. Following intraperitoneal injection of colchicine, aged rats exhibited a significant increase in S100A4-positive neurons in the ENS 24 h post-treatment, reaching levels comparable to those in young rats. Quantitative real-time reverse transcription polymerase chain reaction(qRT-qPCR) and Western blot analysis revealed no significant changes in S100A4 mRNA and corresponding protein levels in the muscularis propria and submucosa of the colon, small intestine, and stomach between young and aged rats.

conclusion​ S100A4 is widely and specifically localized within neurons of the rat gastrointestinal nervous system, with all S100A4 neurons expressing calretinin. In aged enteric neurons, S100A4 is transported from the cell body to neuronal processes and nerve endings, indicating a dynamic redistribution rather than mere depletion during aging.

Indexed as

AgingEnteric Nervous SystemS100 Calcium-Binding Protein A4S100 ProteinsAnimalsCalbindin 2Choline O-AcetyltransferaseColchicineELAV ProteinsGastrointestinal TractMaleNeuronsRatsRats, WistarCalbindin 2Choline O-AcetyltransferaseColchicineELAV ProteinsS100a4 protein, ratS100 Calcium-Binding Protein A4S100 ProteinsAgingEnteric Nervous SystemRat​ S100A4

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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 OpenQuestion graph.