Compensatory role of C3 convertase on the strain difference for C3 protein expression in FVB/N, C3H/HeN and C57BL/6N mice

Park, Ji Won; Kim, Ji Eun; Kang, Mi Ju; Choi, Hak Jong; Bae, Su Ji; Hwang, Dae Youn

doi:10.1186/s42826-020-0036-7

Cited by 4 publications

(5 citation statements)

References 19 publications

(14 reference statements)

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“…Also, a similar alteration mechanism on activation of G proteins was detected during C3-deficiency-induced constipation. The normal function of the gastrointestinal tract may be suppressed through the dysregulation of C3a receptor mediated signaling pathways due to this receptor being one of the members of the GPCRs [44][45][46]. Furthermore, alterations on the receptor signaling pathway for two neurotransmitters, 5-HT and muscarinic acetylcholine, was investigated during the investigation of the therapeutic effects of Urd in the constipation model.…”

Section: Discussionmentioning

confidence: 99%

Complement C3-Deficiency-Induced Constipation in FVB/N-C3em1Hlee/Korl Knockout Mice Was Significantly Relieved by Uridine and Liriope platyphylla L. Extracts

Song,

Kim,

Jin

et al. 2023

IJMS

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Complement component 3 (C3) deficiency has recently been known as a cause of constipation, without studies on the therapeutic efficacy. To evaluate the therapeutic agents against C3-deficiency-induced constipation, improvements in the constipation-related parameters and the associated molecular mechanisms were examined in FVB/N-C3em1Hlee/Korl knockout (C3 KO) mice treated with uridine (Urd) and the aqueous extract of Liriope platyphylla L. (AEtLP) with laxative activity. The stool parameters and gastrointestinal (GI) transit were increased in Urd- and AEtLP-treated C3 KO mice compared with the vehicle (Veh)-treated C3 KO mice. Urd and AEtLP treatment improved the histological structure, junctional complexes of the intestinal epithelial barrier (IEB), mucin secretion ability, and water retention capacity. Also, an improvement in the composition of neuronal cells, the regulation of excitatory function mediated via the 5-hydroxytryptamine (5-HT) receptors and muscarinic acetylcholine receptors (mAChRs), and the regulation of the inhibitory function mediated via the neuronal nitric oxide synthase (nNOS) and inducible NOS (iNOS) were detected in the enteric nervous system (ENS) of Urd- and AEtLP-treated C3 KO mice. Therefore, the results of the present study suggest that C3-deficiency-induced constipation can improve with treatment with Urd and AEtLP via the regulation of the mucin secretion ability, water retention capacity, and ENS function.

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Section: Discussionmentioning

confidence: 99%

Complement C3-Deficiency-Induced Constipation in FVB/N-C3em1Hlee/Korl Knockout Mice Was Significantly Relieved by Uridine and Liriope platyphylla L. Extracts

Song,

Kim,

Jin

et al. 2023

IJMS

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“…Lastly, the C3 receptors, including CR1, CR2, CR3, and CR4, contribute to the migration and phagocytosis of cells and immune regulation through binding with several C3 fragments, such as C3a, iC3b, C3d, and C3f [ 54 , 55 ]. Significant alterations in the expression of these receptors have been detected in various diseases, such as inflammatory diseases [ 56 , 57 ], vascular disease [ 58 ], and microbial infection, even though C3bα and β-protein were maintained consistently in several strains of mice [ 59 , 60 ]. On the other hand, these changes in constipation conditions have been examined in limited studies.…”

Section: Discussionmentioning

confidence: 99%

Dysregulation of the Enteric Nervous System in the Mid Colon of Complement Component 3 Knockout Mice with Constipation Phenotypes

Choi

Song

Kim

et al. 2022

IJMS

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Complement component 3 (C3) contributes to neurogenesis, neural migration, and synaptic elimination under normal and disease conditions of the brain, even though it has not been studied in the enteric nervous system (ENS). To determine the role of C3 in the regulatory mechanism of ENS during C3 deficiency-induced constipation, the changes in the markers of neuronal and interstitial cells of Cajal (ICCs), the markers for excitatory and inhibitory transmission of ENS, and expression of C3 receptors were analyzed in the mid colon of C3 knockout (KO) mice at 16 weeks of age. Prominent constipation phenotypes, including the decrease in stool parameters, changes in the histological structure, and suppression of mucin secretion, were detected in C3 KO mice compared to wildtype (WT) mice. The expression levels of the neuron specific enolase (NSE), protein gene product 9.5 (PGP9.5), and C-kit markers for myenteric neurons and ICCs were lower in the mid colon of C3 KO mice than WT mice. Excitatory transmission analysis revealed similar suppression of the 5-hydroxytryptamine (5-HT) concentration, expression of 5-HT receptors, acetylcholine (ACh) concentration, ACh esterase (AChE) activity, and expression of muscarinic ACh receptors (mAChRs), despite the mAChRs downstream signaling pathway being activated in the mid colon of C3 KO mice. In inhibitory transmission analysis, C3 KO mice showed an increase in the nitric oxide (NO) concentration and inducible nitric oxide synthase (iNOS) expression, while neuronal NOS (nNOS) expression, cholecystokinin (CCK), and gastrin concentration were decreased in the same mice. Furthermore, the levels of C3a receptor (C3aR) and C3bR expression were enhanced in the mid colon of C3 KO mice compared to the WT mice during C3 deficiency-induced constipation. Overall, these results indicate that a dysregulation of the ENS may play an important role in C3 deficiency-induced constipation in the mid colon of C3 KO mice.

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“…34,35 Recently, immunological differences have been described in the function of C3 convertase between the C57BL/6 and FVB/N strains. 36 Numerous differences were observed between the strains, including the expression of several common Treg markers, as well as a functional difference between FVB/N T A B L E 1 PubMed search results for Treg terms and strain and C57BL/6 mice. Understanding the differences in the immune responses of various mouse strains has become increasingly important as Tregs are now the target of therapeutics in a much more genetically diverse human population.…”

Section: Introductionmentioning

confidence: 99%

“…Biologically relevant differences have also been described between the C57BL/6 and the FVB/N in the development of diabetes and obesity 34,35 . Recently, immunological differences have been described in the function of C3 convertase between the C57BL/6 and FVB/N strains 36 …”

Section: Introductionmentioning

confidence: 99%

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FVB/N mouse strain regulatory T cells differ in phenotype and function from the C57BL/6 and BALB/C strains

Tanner

Lorenz

2022

FASEB BioAdvances

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Regulatory T cells (Treg) are vital to the maintenance of immune homeostasis. The genetic background of an inbred mouse strain can have a profound effect on the immune response in the animal, including Treg responses. Most Treg studies focus on animals created on the C57BL/6 or BALB/c background. Recent studies have demonstrated a difference in the phenotype and behavior of C57BL/6 and BALB/c Tregs. In this study, we have investigated the function of FVB/N Tregs compared to C57BL/6 and BALB/c. We observed that while FVB/N Tregs appear to suppress normally in a cell contact‐dependent system, FVB/N Tregs are less capable of suppressing when regulation depends on the secretion of a soluble factor. FVB/N Tregs produce IL‐10; however, TGF‐β was not detected in any culture from C57BL/6 or FVB/N. C57BL/6 Foxp3+ Tregs expressed more of the TGF‐β‐related proteins glycoprotein‐A repetitions predominant (GARP) and latency‐associated peptide (LAP) on the cell surface than both FVB/N and BALB/c, but C57BL/6 Tregs expressed significantly less Ctse (Cathepsin E) mRNA. Each strain displayed different abilities of thymic Tregs (tTreg) to maintain Foxp3 expression and had a varying generation of induced Tregs (iTregs). In vitro generated FVB/N iTregs expressed significantly less GARP and LAP. These results suggest Tregs of different strains have varying phenotypes and dominant mechanisms of action for the suppression of an immune response. This information should be taken into consideration when Tregs are examined in future studies, particularly for therapeutic purposes in a genetically diverse population.

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Compensatory role of C3 convertase on the strain difference for C3 protein expression in FVB/N, C3H/HeN and C57BL/6N mice

Cited by 4 publications

References 19 publications

Complement C3-Deficiency-Induced Constipation in FVB/N-C3em1Hlee/Korl Knockout Mice Was Significantly Relieved by Uridine and Liriope platyphylla L. Extracts

Complement C3-Deficiency-Induced Constipation in FVB/N-C3em1Hlee/Korl Knockout Mice Was Significantly Relieved by Uridine and Liriope platyphylla L. Extracts

Dysregulation of the Enteric Nervous System in the Mid Colon of Complement Component 3 Knockout Mice with Constipation Phenotypes

FVB/N mouse strain regulatory T cells differ in phenotype and function from the C57BL/6 and BALB/C strains

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