Dataset Information

Dermal mesenchymal stem cells: a resource of migration-associated function in psoriasis?

ABSTRACT:

Background

Psoriasis is a chronic and systemic, immune-mediated, inflammatory disease. Mesenchymal stem cells have effects on the inflammatory microenvironment, including regulating the proliferation, differentiation, recruitment, and migration of immunocytes.

Methods

To investigate whether dermal mesenchymal stem cells (DMSCs) may act on migration of immunocytes in psoriasis patients, 22 patients with psoriasis and 22 matching healthy controls (age and sex in this study) were recruited. Seven migration-associated genes including chemokine like receptor-1 (CMKLR-1), collagen type VIII alpha1 (COL8A-1), neuropilin and tolloid-like 2 (NETO-2), nik-related kinase (NRK), secreted frizzled-related protein (SFRP), sulfate 6-O-endosulfatase 2 (SULF-2), and synaptotagmin-like protein 2 (SYTL-2) were analyzed by quantitative real-time reverse transcription PCR and western blot. Peripheral blood-derived mononuclear cells (PBMCs) migration to MSCs was measured using a Thanswell chamber system.

Results

We observed the upregulation of CMKLR-1, COL8A-1, NETO-2, NRK, SYTL-2, and SULF-2 in dermal mesenchymal stem cells derived from patients with psoriasis at both mRNA and protein level, however, a significant downregulation of SFRP-2 between two groups. By contrast, there were no significant between-group differences at the mRNA and protein expression level of NETO-2 and SULF-2. The migration assay showed that in vitro the normal PBMC migration to psoriatic DMSC group was a 6.3 ± 0.7-fold increase compared with the control group.

Conclusions

The results may suggest a potential pathogenetic involvement of DMSCs on migration of monocytes in psoriasis. Immune responses are regulated at the level of DMSCs, which probably represent the cells primarily involved in the "psoriatic march."

SUBMITTER: Niu X

PROVIDER: S-EPMC6375130 | biostudies-literature | 2019 Feb

REPOSITORIES: biostudies-literature

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Publications

Dermal mesenchymal stem cells: a resource of migration-associated function in psoriasis?

Niu Xuping X Li Junqing J Zhao Xincheng X Wang Qiang Q Wang Gang G Hou Ruixia R Li Xinhua X An Peng P Yin Guohua G Zhang Kaiming K

Stem cell research & therapy 20190213 1

<h4>Background</h4>Psoriasis is a chronic and systemic, immune-mediated, inflammatory disease. Mesenchymal stem cells have effects on the inflammatory microenvironment, including regulating the proliferation, differentiation, recruitment, and migration of immunocytes.<h4>Methods</h4>To investigate whether dermal mesenchymal stem cells (DMSCs) may act on migration of immunocytes in psoriasis patients, 22 patients with psoriasis and 22 matching healthy controls (age and sex in this study) were rec ...[more]

PMID: 30760317

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Project description:BackgroundThe function of exosomes, small extracellular vesicles (sEV) secreted from human adipose-derived stem cells (ADSC), is becoming increasingly recognized as a means of transferring the regenerative power of stem cells to injured cells in wound healing. Exosomes are rich in ceramides and long noncoding RNA (lncRNA) like metastasis-associated lung adenocarcinoma transcript 1 (MALAT1). We identified putative ceramide responsive cis-elements (CRCE) in MALAT1. We hypothesized that CRCE respond to cellular ceramide levels to regulate sEV MALAT1 packaging. MALAT1 levels by many cells exceed those of protein coding genes and it's expression is equally high in exosomes. Ceramide also regulates exosome synthesis, however, the contents of exosome cargo via sphingomyelinase and ceramide synthase pathways has not been demonstrated.MethodsADSC were treated with an inhibitor of sphingomyelinase, GW4869, and stimulators of ceramide synthesis, C2- and C6-short chain ceramides, prior to collection of conditioned media (CM). sEV were isolated from CM, and then used to treat human dermal fibroblast (HDF) cultures in cell migration scratch assays, and mitochondrial stress tests to evaluate oxygen consumption rates (OCR).ResultsInhibition of sphingomyelinase by treatment of ADSC with GW4869 lowered levels of MALAT1 in small EVs. Stimulation of ceramide synthesis using C2- and C6- ceramides increased cellular, EVs levels of MALAT1. The functional role of sEV MALAT1 was evaluated in HDF by applying EVs to HDF. Control sEV increased migration of HDF, and significantly increased ATP production, basal and maximal respiration OCR. sEV from GW4869-treated ADSC inhibited cell migration and maximal respiration. However, sEV from C2- and C6-treated cells, respectively, increased both functions but not significantly above control EV except for maximal respiration. sEV were exosomes except when ADSC were treated with GW4869 and C6-ceramide, then they were larger and considered microvesicles.ConclusionsCeramide synthesis regulates MALAT1 EV content. Sphingomyelinase inhibition blocked MALAT1 from being secreted from ADSC EVs. Our report is consistent with those of MALAT1 increasing cell migration and mitochondrial MALAT1 altering maximal respiration in cells. Since MALAT1 is important for exosome function, it stands that increased exosomal MALAT1 should be beneficial for wound healing as shown with these assays. Video Abstract.

Dataset Information

Dermal mesenchymal stem cells: a resource of migration-associated function in psoriasis?

Background

Methods

Results

Conclusions

Publications

Dermal mesenchymal stem cells: a resource of migration-associated function in psoriasis?

Similar Datasets

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