Investigation of autophagy and differentiation of myenteric interstitial cells of Cajal in the pathogenesis of gastric motility disorders in rats with functional dyspepsia

Zhang, Limin; Zeng, Lijun; Deng, Jing; Zhang, Yuqin; Wang, Yujiao; Xie, Tong; Ling, Jianghong

doi:10.1002/bab.1635

Cited by 23 publications

(11 citation statements)

References 30 publications

(30 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Based on the functions of ICCs in generating slow-wave potentials for GI movement, ICC dysfunction can cause many GI motility disorders [ 29 ]. FD is known as one of the representative diseases associated with dysfunction of ICCs [ 30 ]. Abnormal gastric slow waves have been observed in patients with FD via multichannel electrogastrography [ 31 ].…”

Section: Pathophysiologic Involvement Of Icc In Fdmentioning

confidence: 99%

“…Pathological findings have shown that delayed gastric dysmotility is associated with degeneration of ICCs in both humans [ 32 ] and animals [ 33 ]. In an FD rat model induced by chronic stress via tail clamping, the levels of autophagic biomarkers in ICCs were increased, whereas the levels of differentiation biomarkers in ICCs, such as c-kit and SCF, were decreased [ 30 ]. Although the relationship between ICC dysfunction and FD has not been accurately elucidated, excessive autophagy and abnormal differentiation of ICCs seem to contribute to the pathogenesis of FD [ 11 ].…”

Section: Pathophysiologic Involvement Of Icc In Fdmentioning

confidence: 99%

See 1 more Smart Citation

Interstitial Cells of Cajal: Potential Targets for Functional Dyspepsia Treatment Using Medicinal Natural Products

Joung

Choi²,

Son

2021

Evidence-Based Complementary and Alternative Medicine

View full text Add to dashboard Cite

Introduction. The pathophysiology of functional dyspepsia (FD) remains uncertain, but the interstitial cells of Cajal (ICCs), pacemakers that regulate gastrointestinal motility, are garnering attention as key modulators and therapeutic targets in FD. This review comprehensively discusses the involvement of ICCs in the pharmacologic actions of FD and as therapeutic targets for herbal products for FD. Methods. A search of the literature was performed using PubMed by pairing “interstitial cells of Cajal” with “medicinal plant, herbal medicine, phytotherapy, flavonoids, or traditional Chinese medicine (TCM).” Results. From the 55 articles screened in the initial survey, 34 articles met our study criteria. The search results showed that herbal products can directly depolarize ICCs to generate pacemaker potentials and increase the expression of c-kit and stem cell factors, helping to repair ICCs. Under certain pathological conditions, medicinal plants also protect ICCs from oxidative stress and/or inflammation-induced impairment. Two representative herbal decoctions (Banhasasim-tang, 半夏泻心汤, and Yukgunja-tang, 六君子汤) have been shown to modulate ICC functions by both clinical and preclinical data. Conclusion. This review strongly indicates the potential of herbal products to target ICCs and suggests that further ICC-based studies would be promising for the development of FD treatment agents.

show abstract

Section: Pathophysiologic Involvement Of Icc In Fdmentioning

confidence: 99%

Section: Pathophysiologic Involvement Of Icc In Fdmentioning

confidence: 99%

Interstitial Cells of Cajal: Potential Targets for Functional Dyspepsia Treatment Using Medicinal Natural Products

Joung

Choi²,

Son

2021

Evidence-Based Complementary and Alternative Medicine

View full text Add to dashboard Cite

show abstract

“…15 Besides, a study by Zhang et al reported that excessive autophagy of myenteric ICCs may contribute to the pathogenesis of gastric motility disorder in functional dyspepsia. 16 Most importantly, Yan et al found that Aurantii Fructus Immaturus (Zhishi, ZS) and Atractylodis Macrocephalae Rhizoma (Baizhu, BZ)-containing serum significantly inhibited autophagy through inactivation of the PI3K/Akt/mTOR pathway in glutamic acid-stimulated ICCs. 17 Additionally, another research reported that the inflammasome plays a crucial role in gastrointestinal health and disease.…”

Section: Introductionmentioning

confidence: 99%

METTL3 contributes to slow transit constipation by regulating miR‐30b‐5p/PIK3R2/Akt/mTOR signaling cascade through DGCR8

Gong

Dai

et al. 2022

J of Gastro and Hepatol

View full text Add to dashboard Cite

Background N6‐methyladenosine (m6A) is the most prevalent methylation modification of eukaryotic RNA, and methyltransferase‐like 3 (METTL3) plays a vital role in multiple cell functions. This study aimed to investigate the role of m6A methylase METTL3 in slow transit constipation (STC). Material and Method The expression of METTL3 and DGCR8 was measured in STC tissues and glutamic acid‐induced interstitial cells of Cajal (ICCs). The effects of METTL3, miR‐30b‐5p, and DGCR8 on the biological characteristics of ICCs were investigated on the basis of loss‐of‐function analyses. Luciferase reporter assay was used to identify the direct binding sites of miR‐30b‐5p with PIK3R2. Results The results showed that the METTL3, DGCR8, miR‐30b‐5p, and the methylation level of m6A were significantly increased in STC tissues and glutamic acid‐induced ICCs. Silencing of METTL3 and miR‐30b‐5p inhibited apoptosis, autophagy, and pyroptosis of glutamic acid‐induced ICCs. Moreover, overexpression of miR‐30b‐5p reversed the cytoprotection of METTL3 knockdown in glutamic acid‐induced ICCs. Besides, DGCR8 knockdown could facilitate cell growth and decrease apoptotic glutamic acid‐induced ICCs. Mechanically, we illustrated that METTL3 in glutamic acid‐induced ICCs significantly accelerated the maturation of pri‐miR‐30b‐5p by m6A methylation modification, resulting in the reduction of PIK3R2, which results in the inhibition of PI3K/Akt/mTOR pathway and ultimately leads to the cell death of STC. Conclusions Collectively, these data demonstrated that METTL3 promoted the apoptosis, autophagy, and pyroptosis of glutamic acid‐induced ICCs by interacting with the DGCR8 and successively modulating the miR‐30b‐5p/PIK3R2 axis in an m6A‐dependent manner, and METTL3 may be a potential therapeutic target for STC.

show abstract

“…FD is a representative disease of gastrointestinal motility disorder. ICC will be a possible direction to respond to FD in the future (Zhang et al, 2018). Hawthorn refers to the ripe fruit of Crataegus pinnatifida Bge in the Rosaceae family (Figure 1).…”

Section: Introductionmentioning

confidence: 99%

Investigation of the improving effect of raw and charred hawthorn on functional dyspepsia based on interstitial cells of Cajal

Zhang²,

Liang³

et al. 2022

Front. Sustain. Food Syst.

View full text Add to dashboard Cite

BackgroundRaw hawthorn (RH) is a traditional Chinese medicine commonly used to treat indigestion. Charred hawthorn (CH) is obtained from RH by charring. It is reported that the effect of CH treatment on dyspepsia is stronger than RH. However, this has not been fully proven. The purpose of this study was to compare the effects of RH and CH on functional dyspepsia (FD) model rats. And contribute to the development of dietary therapy for dyspepsia.MethodsSPF-grade male SD rats were divided into 5 groups: the control group, the model group, the Mos group, the RH group, and the CH group. The FD rat model was established by using the methods of water restriction, fasting, tilting cage restraint, day and night upside down, swimming, and tail damping. The body weight of rats in each group was recorded. And the gastric emptying rate, intestinal propulsive rate, and the levels of motilin (MTL), gastrin (GAS), and 5-HT in serum were compared in each group. The expression of C-kit in the stomach and small intestine of each group was compared by immunofluorescence and PCR.ResultsRH and CH could increase weight, improve the gastric emptying rate and intestinal propulsive rate, and promote the secretion of motilin (MTL), gastrin (GAS), and 5-HT in the serum of FD rats. RH and CH can upregulate the expression of the characteristic protein c-kit of ICC in the stomach and small intestine of FD model rats, and the effect of CH is stronger than RH.ConclusionRH and CH may increase the number of interstitial cells of Cajal (ICC) in the gastrointestinal tract by upregulating c-kit expression, thus improving gastrointestinal motility in FD model rats. And compared with RH, CH has certain advantages.

show abstract

Investigation of autophagy and differentiation of myenteric interstitial cells of Cajal in the pathogenesis of gastric motility disorders in rats with functional dyspepsia

Cited by 23 publications

References 30 publications

Interstitial Cells of Cajal: Potential Targets for Functional Dyspepsia Treatment Using Medicinal Natural Products

Interstitial Cells of Cajal: Potential Targets for Functional Dyspepsia Treatment Using Medicinal Natural Products

METTL3 contributes to slow transit constipation by regulating miR‐30b‐5p/PIK3R2/Akt/mTOR signaling cascade through DGCR8

Investigation of the improving effect of raw and charred hawthorn on functional dyspepsia based on interstitial cells of Cajal

Contact Info

Product

Resources

About