Int J Stem Cells.  2021 Feb;14(1):85-93. 10.15283/ijsc20073.

Dysregulated Dermal Mesenchymal Stem Cell Proliferation and Differentiation Interfered by Glucose Metabolism in Psoriasis

• Zhao X
• Xing J
• Li J
• Hou R
• Niu X
• Liu R
• Jiao J
• Yang X
• Li J
• Liang J
• Zhou L
• Wang Q
• Chang W
• Yin G
• Li X
• Zhang K

• KMID: 2513085
• DOI: http://doi.org/10.15283/ijsc20073

Abstract

Background and Objectives
Psoriasis is a chronic inflammatory skin disease, which the mechanisms behind its initiation and development are related to many factors. DMSCs (dermal mesenchymal stem cells) represent an important member of the skin microenvironment and play an important role in the surrounding environment and in neighbouring cells, but they are also affected by the microenvironment. We studied the glucose metabolism of DMSCs in psoriasis patients and a control group to reveal the relationship among glucose metabolism, cell proliferation activity，and VEC (vascular endothelial cell) differentiation in vitro, we demonstrated the biological activity and molecular mechanisms of DMSCs in psoriasis.
Methods and Results
We found that the OCR of DMSCs in psoriatic lesions was higher than that in the control group, and mRNA of GLUT1 and HK2 were up-regulated compared with the control group. The proliferative activity of DMSCs in psoriasis was reduced at an early stage, and mRNA involved in proliferation, JUNB and FOS were expressed at lower levels than those in the control group. The number of blood vessels in psoriatic lesions was significantly higher than that in the control group (p＜0.05), which the mRNA of VEC differentiation, CXCL12, CXCR7, HEYL and RGS5 tended to be increased in psoriatic lesions compared to the control group, in addition to Notch3.
Conclusions
We speculated that DMSCs affected local psoriatic blood vessels through glucose metabolism, and the differentiation of VECs, which resulted in the pathophysiological process of psoriasis.

Keyword

Cell proliferation; DMSCs; Glucose metabolism; Psoriasis; Vascular differention

Figure

• 

  Fig. 1 The metabolic profile of DMSCs. Basal OCR was measured before oligomycin treatment, and it was subtracted after rotenone/antimycin treatment. (A) ATP-linked OCR was calculated by subtracting the basal OCR from the amount of respiration left after oligomycin was added. Proton leakage was determined by subtracting the non-mitochondrial OCR from the amount of respiration left after oligomycin was added. Maximal respiration was calculated by subtracting the maximal OCR from the non-mitochondrial OCR. The reserve capacity was determined by subtracting the maximal OCR from the basal OCR. (B) O2 consumption in the DMSCs of the psoriasis and control groups. The rates of O2 (OCR) were first measured in DMSCs under basal conditions and then sequentially after the addition of oligomycin (1 µM), carbonylcyanidep-(trifluoromethoxy), phenylhydrazone (FCCP) (2 μM), and rotenone (0.5 μM). (C) Graphs show the ATP-linked OCR, proton leak OCR, maximal OCR, reserve capacity and non-mitochondrial OCR in the psoriasis and control groups. (D, E) Histograms showing the relative mRNA expression levels of GLUT1 and HK2. ns p>0.05, *p< 0.05, ***p<0.001.

• 

  Fig. 2 Identification of DMSCs. (A∼C) Morphological characteristics of DMSCs cultured for 6, 12 and 15 days (×200). (D, E) Morphology of adipocytes and osteoblasts generated by the induction of DMSCs; adipocytes stained before; adipocytes stained with oil red O; osteoblasts stained before; osteoblasts stained with alizarin red (×400). (F) Angiogenic network in DMSCs after differentiation (×400). Overlay of ac-LDL and UEA-1 in DMSCs after differentiation, the uptake of ac-LDL stimulated red fluorescence, the UEA-1stimulated green fluorescence, and the ac-LDL and UEA-1stimulated red and green fluorescence (×200). (G) Identification of DMSCs by flow cytometry.

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  Fig. 3 The proliferation potential of DMSCs. (A, B) The number of normal control DMSCs and psoriatic DMSCs; during long-term culture; on the 3 day. (C, D) JUNB and FOS mRNA expression (psoriasis/control) in the psoriasis and control groups. ns p>0.05, *p<0.05, ***p<0.001.

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  Fig. 4 The number of local blood vessels and the expression of mRNA related to VEC differentiation in the psoriasis and control groups. (A∼D) Histopathology skin tissue by haematoxylin and eosin (HE) staining as seen under a microscope; A&B were psoriatic lesions; C&D were control skin tissue (A&C ×200 and B＆D ×400, respectively). (E) Blood vessel counts between the psoriasis and control groups. (F) HEYL, CXCR7, CXCL12, RGS5 and Notch3 mRNA relative expression. ***p<0.001.

Reference

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