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. 2023 Jun 2:14:1131993.
doi: 10.3389/fendo.2023.1131993. eCollection 2023.

Changes and related factors of blood CCN1 levels in diabetic patients

Zhao-Yu Xiang  1   2 , Shu-Li Chen  1   2 , Xin-Ran Qin  1   2 , Sen-Lin Lin  2 , Yi Xu  2 , Li-Na Lu  2 , Hai-Dong Zou  1   2
Affiliations

Changes and related factors of blood CCN1 levels in diabetic patients

Zhao-Yu Xiang et al. Front Endocrinol (Lausanne). .

Abstract

Objective: To study the differences in blood cellular communication network factor 1 (CCN1) levels between patients with diabetes mellitus (DM) and healthy individuals and to explore the relationship between CCN1 and diabetic retinopathy (DR).

Methods: Plasma CCN1 levels were detected using ELISA in 50 healthy controls, 74 patients with diabetes without diabetic retinopathy (DM group), and 69 patients with diabetic retinopathy (DR group). Correlations between CCN1 levels and age, body mass index, mean arterial pressure, hemoglobin A1c, and other factors were analyzed. The relationship between CCN1 expression and DR was explored using logistic regression after adjusting for confounding factors. Blood mRNA sequencing analysis was performed for all subjects, and the molecular changes that may be related to CCN1 were explored. The retinal vasculature of streptozotocin-induced diabetic rats was examined using fundus fluorescein angiography; in addition, retinal protein expression was examined using western blotting.

Results: Plasma CCN1 levels in patients with DR were significantly higher than in the control and DM groups; however, no significant differences were observed between healthy controls and patients with DM. CCN1 levels negatively correlated with body mass index and positively correlated with the duration of diabetes and urea levels. It was observed that high (OR 4.72, 95% CI: 1.10-20.25) and very high (OR 8.54, 95% CI: 2.00-36.51) levels of CCN1 were risk factors for DR. Blood mRNA sequencing analysis revealed that CCN1-related pathways were significantly altered in the DR group. The expression of hypoxia-, oxidative stress-, and dephosphorylation-related proteins were elevated, while that of tight junction proteins were reduced in the retinas of diabetic rats.

Conclusion: Blood CCN1 levels are significantly elevated in patients with DR. High and very high levels of plasma CCN1 are risk factors for DR. Blood CCN1 level may be a potential biomarker for diagnosis of DR. The effects of CCN1 on DR may be related to hypoxia, oxidative stress, and dephosphorylation.

Keywords: CCN1/Cyr61; blood biomarker; blood-retinal barrier; diabetic Retinopathy; diabetic complications.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Receiver operating characteristic curve of DR DR, Diabetic Retinopathy; CCN1, Cellular Communication Network Factor 1; HbA1c, Hemoglobin A1c; AUC, Area Under Curve.
Figure 2
Figure 2
Differences in the retina between diabetic and non-diabetic rats. (A) Fundus fluorescein angiography of diabetic and non-diabetic rats. (B) Differences in protein expression levels between diabetic and non-diabetic rats. (C) Western blotting strip images of diabetic and non-diabetic rats. CCN1, Cellular Communication Network Factor 1; COX6c, cytochrome c oxidase subunit 6c; CREB1, Cyclic AMP-responsive element-binding protein1; HIF1α, Hypoxia-inducible factor 1α; NDUFα1, NADH dehydrogenase 1 alpha subcomplex; SEPN1, Selenoprotein N 1; SHP1, Protein-tyrosine phosphatase 1C; VEGFa, vascular endothelial growth factor a; Differences between control and diabetic rats were compared using the Mann–Whitney test, and the values of protein expression were analyzed using β-tubulin as the internal control; *p< 0.05, compared with controls.
See this image and copyright information in PMC

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