Monogenic deficiency in murine intestinal Cdc42 leads to mucosal inflammation that induces crypt dysplasia

Zhang, Dongsheng; Tang, Wenjuan; Niu, Haitao; Tse, William Ka Fai; Ruan, Hai‐Bin; Dolznig, Helmut; Knösel, Thomas; Karl-Heinz, Friedrich; Themanns, Madeleine; Wang, Jiang; Song, Moon Hee; Denson, Lee A.; Kenner, Lukas; Moriggl, Richard; Zheng, Yi; Han, Xiaonan

doi:10.1016/j.gendis.2022.11.024

Cited by 5 publications

(3 citation statements)

References 64 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The copyright holder for this preprint this version posted March 22, 2024. ; https://doi.org/10.1101/2024.03.21.586086 doi: bioRxiv preprint processes, including cell division, intracellular transport, gene transcription, cell cycle regulation, and regulates cell growth and stability. [29][30][31] We overexpressed miR-206 within VEGFA-treated BM-MSCs to detect the expression levels of CDC42 gene and protein in the cells. It was found that the expression of CDC42 was down-regulated in cells transfected with miR-206.…”

Section: Discussionmentioning

confidence: 99%

“…All rights reserved. No reuse allowed without permission.The copyright holder for this preprint this version postedMarch 22, 2024. ; https://doi.org/10.1101/2024.03.21.586086 doi: bioRxiv preprintMechanism of MALAT1 in regulating the differentiation of BM-MSCs to ECs.BM-MSCs were treated with VEGFA(20,30, 40, 50 ng/ml) to induce differentiation of BM-MSCs to ECs in vitro. After RT-qPCR to detect miR-206 expression in BM-MSCs, it was found that miR-206 expression in BM-MSCs was lowest at 50 ng/ml VEGFA (Figure5 A).…”

mentioning

confidence: 99%

See 1 more Smart Citation

MALAT1 mediates miR-206/CDC42/PAK1/Paxillin signaling axis to alleviate erectile dysfunction in rats

Luo,

Wang,

Tong

et al. 2024

Preprint

View full text Add to dashboard Cite

Erectile dysfunction (ED) is a male sexual dysfunction with a gradually increasing prevalence, and current treatments are ineffective. This study aims to find a safer and more effective treatment for erectile dysfunction. Bone marrow-derived mesenchymal stem cells (BM-MSCs) treated with VEGFA. The expression of endothelial markers vWF, VE-cadherin and eNOS were determined by overexpressing MALAT1 and CDC42, respectively. The results showed that interference with CDC42 and MALAT1 expression inhibited the differentiation of BM-MSCs to ECs and the expression of endothelial marker-related proteins. Moreover, MALAT1 induced differentiation of BM-MCs to ECs through the CDC42/PAK1/Paxillin pathway was explored by transfecting si-MALAT1 and overexpressing CDC42 as well as PAK1 in the BM-MSCs. Next, miR-206 was overexpressed within BM-MCs to determine CDC42 expression. The binding sites of MALAT1, miR-206 and CDC42 were reported using luciferase. it was found that the MALAT1 competes with CDC42 3'-UTR for binding miR-206, which in turn is involved in differentiating BM-MSCs to ECs. Finally, DMED rat modeling success was demonstrated by APO experiments. MALAT1 overexpression-modified BM-MSCs had significant therapeutic effects in DMED rats.

show abstract

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

MALAT1 mediates miR-206/CDC42/PAK1/Paxillin signaling axis to alleviate erectile dysfunction in rats

Luo,

Wang,

Tong

et al. 2024

Preprint

View full text Add to dashboard Cite

show abstract

“…In recent years, microRNAs have been found to play a wide range of physiological regulatory roles [35]. In the Rho family, CDC42 is a protein with GTPase activity that is involved in various physiological processes, including cell division, intracellular transport, gene transcription, cell cycle, cell growth, and cell stability [36][37][38]. The CDC42 3'-UTR has a binding site for miR-206.…”

Section: Discussionmentioning

confidence: 99%

LncRNA MALAT1 facilitates BM-MSCs differentiation into endothelial cells and ameliorates erectile dysfunction via the miR-206/CDC42/PAK1/paxillin signalling axis

Luo,

Wang,

Tong

et al. 2024

Reprod Biol Endocrinol

View full text Add to dashboard Cite

Background Erectile dysfunction (ED) is a common male sexual dysfunction, with an increasing incidence, and the current treatment is often ineffective. Methods Vascular endothelial growth factor (VEGFA) was used to treat bone marrow-derived mesenchymal stem cells (BM-MSCs), and their cell migration rates were determined by Transwell assays. The expression of the von Willebrand Factor (vWF)VE-cadherin, and endothelial nitric oxide synthase(eNOS) endothelial markers was determined by qRT‒PCR and Western blot analyses. The MALAT1-induced differentiation of BM-MCs to ECs via the CDC42/PAK1/paxillin pathway was explored by transfecting VEGFA-induced BM-MSC with si-MALAT1 and overexpressing CDC42 and PAK1. The binding capacity between CDC42, PAK1, and paxillin in VEGFA-treated and non-VEGFA-treated BM-MSCs was examined by protein immunoprecipitation. MiR-206 was overexpressed in VEGFA-induced BM-MSC, and the binding sites of MALAT1, miR-206, and CDC42 were identified using a luciferase assay. Sixty male Sprague‒Dawley rats were divided into six groups (n = 10/group). DMED modelling was demonstrated by APO experiments and was assessed by measuring blood glucose levels. Erectile function was assessed by measuring the intracavernosa pressure (ICP) and mean arterial pressure (MAP). Penile erectile tissue was analysed by qRT‒PCR, Western blot analysis, and immunohistochemical staining. Results MALAT1 under VEGFA treatment conditions regulates the differentiation of BM-MSCs into ECs by modulating the CDC42/PAK1/paxillin axis. In vitro experiments demonstrated that interference with CDC42 and MALAT1 expression inhibited the differentiation of BM-MSCs to ECs. CDC42 binds to PAK1, and PAK1 binds to paxillin. In addition, CDC42 in the VEGFA group had a greater ability to bind to PAK1, whereas PAK1 in the VEGFA group had a greater ability to bind to paxillin. Overexpression of miR-206 in VEGFA-induced BM-MSCs demonstrated that MALAT1 competes with the CDC42 3’-UTR for binding to miR-206, which in turn is involved in the differentiation of BM-MSCs to ECs. Compared to the DMED model group, the ICP/MAP ratio was significantly greater in the three BM-MSCs treatment groups. Conclusions MALAT1 facilitates BM-MSC differentiation into ECs by regulating the miR-206/CDC42/PAK1/paxillin axis to improve ED. The present findings revealed the vital role of MALAT1 in the repair of BM-MSCs for erectile function and provided new mechanistic insights into the BM-MSC-mediated repair of DMED.

show abstract

Cell Division Cycle 42 Improves Renal Functions, Fibrosis, Th1/Th17 Infiltration and Inflammation to Some Degree in Diabetic Nephropathy

Zhao,

Feng,

Zhang

et al. 2024

Inflammation

View full text Add to dashboard Cite

Monogenic deficiency in murine intestinal Cdc42 leads to mucosal inflammation that induces crypt dysplasia

Cited by 5 publications

References 64 publications

MALAT1 mediates miR-206/CDC42/PAK1/Paxillin signaling axis to alleviate erectile dysfunction in rats

MALAT1 mediates miR-206/CDC42/PAK1/Paxillin signaling axis to alleviate erectile dysfunction in rats

LncRNA MALAT1 facilitates BM-MSCs differentiation into endothelial cells and ameliorates erectile dysfunction via the miR-206/CDC42/PAK1/paxillin signalling axis

Cell Division Cycle 42 Improves Renal Functions, Fibrosis, Th1/Th17 Infiltration and Inflammation to Some Degree in Diabetic Nephropathy

Contact Info

Product

Resources

About