miR-195-5p Regulates Tight Junctions Expression via Claudin-2 Downregulation in Ulcerative Colitis

Scalavino, Viviana; Piccinno, Emanuele; Lacalamita, Antonio; Tafaro, Angela; Armentano, Ricardo L.; Giannelli, Gianluigi; Serino, Grazia

doi:10.3390/biomedicines10040919

Cited by 11 publications

(12 citation statements)

References 41 publications

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“…Recently, roles for miR-195-5p have been reported in many diseases such as preeclampsia ( Zhou et al, 2022 ), inflammatory bowel disease ( Scalavino et al, 2022b ), cerebral ischemia-reperfusion (I/R) injury ( Ren et al, 2021 ) and colorectal cancer ( Lin et al, 2019 ). miR-195-5p is a critical regulator of many biological events such as cell proliferation and invasion ( Wang et al, 2021 ), oxidative stress ( Xia et al, 2022 ) and redistribution of tight junctions ( Scalavino et al, 2022a ).…”

Section: Introductionmentioning

confidence: 99%

Regulation of Schwann cell proliferation and migration via miR-195-5p-induced Crebl2 downregulation upon peripheral nerve damage

Zhang

et al. 2023

Front. Cell. Neurosci.

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BackgroundSchwann cells acquire a repair phenotype upon peripheral nerve injury (PNI), generating an optimal microenvironment that drives nerve repair. Multiple microRNAs (miRNAs) show differential expression in the damaged peripheral nerve, with critical regulatory functions in Schwann cell features. This study examined the time-dependent expression of miR-195-5p following PNI and demonstrated a marked dysregulation of miR-195-5p in the damaged sciatic nerve.MethodsCCK-8 and EdU assays were used to evaluate the effect of miR-195-5 on Schwann cell viability and proliferation. Schwann cell migration was tested using Transwell and wound healing assays. The miR-195-5p agomir injection experiment was used to evaluate the function of miR-195-5p in vivo. The potential regulators and effects of miR-195-5p were identified through bioinformatics evaluation. The relationship between miR-195-5p and its target was tested using double fluorescence reporter gene analysis.ResultsIn Schwann cells, high levels of miR-195-5p decreased viability and proliferation, while suppressed levels had the opposite effects. However, elevated miR-195-5p promoted Schwann cell migration determined by the Transwell and wound healing assays. In vivo injection of miR-195-5p agomir into rat sciatic nerves promote axon elongation after peripheral nerve injury by affecting Schwann cell distribution and myelin preservation. Bioinformatic assessment further revealed potential regulators and effectors for miR-195-5p, which were utilized to build a miR-195-5p-centered competing endogenous RNA network. Furthermore, miR-195-5p directly targeted cAMP response element binding protein-like 2 (Crebl2) mRNA via its 3′-untranslated region (3′-UTR) and downregulated Crebl2. Mechanistically, miR-195-5p modulated Schwann cell functions by repressing Crebl2.ConclusionThe above findings suggested a vital role for miR-195-5p/Crebl2 in the regulation of Schwann cell phenotype after sciatic nerve damage, which may contribute to peripheral nerve regeneration.

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Section: Introductionmentioning

confidence: 99%

Regulation of Schwann cell proliferation and migration via miR-195-5p-induced Crebl2 downregulation upon peripheral nerve damage

Zhang

et al. 2023

Front. Cell. Neurosci.

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“…In our recent paper, starting from a miRNA expression profiling of intestinal epithelial cells of an ulcerative colitis mice model, we demonstrated that miR-195-5p resulted downregulated in ulcerative colitis. Moreover, we proved that the intracellular increase of miR-195-5p in colonic epithelial cells led to a decrease of CLDN2 and indirectly, also CLDN1 [ 29 ].…”

Section: Discussionmentioning

confidence: 99%

“…In our recent work, we demonstrated that miR-195-5p was able to maintain barrier integrity, regulating the TJs expression [ 29 ]. In the present study, we aimed to investigate whether miR-195-5p modulates the expression of CLDN2 and the other TJs protein expression also under inflammatory conditions induced by TNF-α stimulation.…”

Section: Introductionmentioning

confidence: 99%

The Increase of miR-195-5p Reduces Intestinal Permeability in Ulcerative Colitis, Modulating Tight Junctions’ Expression

Scalavino

Piccinno

Bianco

et al. 2022

IJMS

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Defects in the intestinal epithelial barrier functions characterize inflammatory conditions such as Inflammatory Bowel Disease (IBD). Overexpression of pro-inflammatory cytokines such as TNF-α, IL-1B, IL-6 and INF-γ trigger epithelial damage. These cytokines are due to upregulation of claudin-2 (CLDN2) that form a pore channel, resulting in redistribution of TJs and an alteration of barrier permeability. Recently, we demonstrated that miR-195-5p is able to regulate CLDN2 and indirectly also CLDN1 in intestinal epithelial cells. Now, we aimed to investigate the modulation of miR-195-5p on the expression of CLDN2 and other TJs under inflammatory conditions induced by TNF-α. We demonstrated that miR-195-5p also modulated the expression of CLDN2 levels after stimulation with TNF-α. In addition, we discovered the role of miR-195-5p in the integrity of the intestinal barrier and in promoting the restoration of the intestinal epithelial. Moreover, we established that replacement of miR-195-5p attenuated the colonic inflammatory response in DSS-induced, colitis and it reduced colonic permeability. In conclusion, our data revealed the role of miR-195-5p in intestinal inflammation in ulcerative colitis, suggesting a potential pharmacological target for new therapeutic approaches.

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“…This increased expression can be attributed to the effect of the inflammatory cytokine IL-6, which is found in abundance in IBD patients [ 124 ]. Conversely, the microRNA miR-195-5p, which is reduced in UC patients in comparison to healthy controls, can impede the expression of these two claudins [ 125 ]. Furthermore, miR-24 is another microRNA that has been revealed to be specifically elevated in the colon tissue and even the blood of UC patients.…”

Section: Leaky Gut and Diseasesmentioning

confidence: 99%

Border Control: The Role of the Microbiome in Regulating Epithelial Barrier Function

Schreiber,

Balas,

Robinson

et al. 2024

Cells

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The gut mucosal epithelium is one of the largest organs in the body and plays a critical role in regulating the crosstalk between the resident microbiome and the host. To this effect, the tight control of what is permitted through this barrier is of high importance. There should be restricted passage of harmful microorganisms and antigens while at the same time allowing the absorption of nutrients and water. An increased gut permeability, or “leaky gut”, has been associated with a variety of diseases ranging from infections, metabolic diseases, and inflammatory and autoimmune diseases to neurological conditions. Several factors can affect gut permeability, including cytokines, dietary components, and the gut microbiome. Here, we discuss how the gut microbiome impacts the permeability of the gut epithelial barrier and how this can be harnessed for therapeutic purposes.

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miR-195-5p Regulates Tight Junctions Expression via Claudin-2 Downregulation in Ulcerative Colitis

Cited by 11 publications

References 41 publications

Regulation of Schwann cell proliferation and migration via miR-195-5p-induced Crebl2 downregulation upon peripheral nerve damage

Regulation of Schwann cell proliferation and migration via miR-195-5p-induced Crebl2 downregulation upon peripheral nerve damage

The Increase of miR-195-5p Reduces Intestinal Permeability in Ulcerative Colitis, Modulating Tight Junctions’ Expression

Border Control: The Role of the Microbiome in Regulating Epithelial Barrier Function

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