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PMC11502962
Gastrointestinal stromal tumors regulate macrophage M2 polarization through the MIF/CXCR4 axis to immune escape.
To further investigate the significant interaction, human ligand–receptor (LR) pairs between cells were analyzed.
PMC11502962
Gastrointestinal stromal tumors regulate macrophage M2 polarization through the MIF/CXCR4 axis to immune escape.
We found that MIF/CXCR4 LR was the most common crosstalk between tumor cells and macrophages in G01 and G02 ( Figures 4 – 6 ).
PMC11502962
Gastrointestinal stromal tumors regulate macrophage M2 polarization through the MIF/CXCR4 axis to immune escape.
Interactions numbers and interaction weights of cell-to-cell. (
PMC11502962
Gastrointestinal stromal tumors regulate macrophage M2 polarization through the MIF/CXCR4 axis to immune escape.
A) Numbers of interactions in G01. (
PMC11502962
Gastrointestinal stromal tumors regulate macrophage M2 polarization through the MIF/CXCR4 axis to immune escape.
B) Weights of interactions in G01. (
PMC11502962
Gastrointestinal stromal tumors regulate macrophage M2 polarization through the MIF/CXCR4 axis to immune escape.
C) Numbers of interactions in G02. (
PMC11502962
Gastrointestinal stromal tumors regulate macrophage M2 polarization through the MIF/CXCR4 axis to immune escape.
D) Weights of interactions in G2.
PMC11502962
Gastrointestinal stromal tumors regulate macrophage M2 polarization through the MIF/CXCR4 axis to immune escape.
G01, high risk GIST; G02, very low risk GIST.
PMC11502962
Gastrointestinal stromal tumors regulate macrophage M2 polarization through the MIF/CXCR4 axis to immune escape.
Outgoing and incoming signaling patterns of Cell-Chat in G01.
PMC11502962
Gastrointestinal stromal tumors regulate macrophage M2 polarization through the MIF/CXCR4 axis to immune escape.
Outgoing and incoming signaling patterns of Cell-Chat in G02.
PMC11502962
Gastrointestinal stromal tumors regulate macrophage M2 polarization through the MIF/CXCR4 axis to immune escape.
MIF/CXCR4 axis was the most crosstalk ligand-receptor between tumor cells and macrophages in G01 (A) and G02 (B).
PMC11502962
Gastrointestinal stromal tumors regulate macrophage M2 polarization through the MIF/CXCR4 axis to immune escape.
LR interactions between tumor cells and other cells play an important role in tumor proliferation, metastasis, and progression.
PMC11502962
Gastrointestinal stromal tumors regulate macrophage M2 polarization through the MIF/CXCR4 axis to immune escape.
Thus, the MIF/CXCR4 signaling axis between tumor cells and macrophages was selected for further investigation.
PMC11502962
Gastrointestinal stromal tumors regulate macrophage M2 polarization through the MIF/CXCR4 axis to immune escape.
In this study, 80 patients were included for immunohistochemistry.
PMC11502962
Gastrointestinal stromal tumors regulate macrophage M2 polarization through the MIF/CXCR4 axis to immune escape.
Their clinicopathological characteristics are presented in Table 3 .
PMC11502962
Gastrointestinal stromal tumors regulate macrophage M2 polarization through the MIF/CXCR4 axis to immune escape.
In these patients, 56 tumors were located in the stomach and 24 tumors were located in the intestine.
PMC11502962
Gastrointestinal stromal tumors regulate macrophage M2 polarization through the MIF/CXCR4 axis to immune escape.
Fourteen patients were classified as the very-low-risk group (LG), 31 patients were classified as the intermediate-risk group (MG), and 35 patients were classified as the high-risk group (HG).
PMC11502962
Gastrointestinal stromal tumors regulate macrophage M2 polarization through the MIF/CXCR4 axis to immune escape.
Clinicopathological characteristics of 80 patients for immunohistochemistry.
PMC11502962
Gastrointestinal stromal tumors regulate macrophage M2 polarization through the MIF/CXCR4 axis to immune escape.
Immunohistochemistry and immunofluorescence were performed ( Figures 7 , 8 ).
PMC11502962
Gastrointestinal stromal tumors regulate macrophage M2 polarization through the MIF/CXCR4 axis to immune escape.
Among the three groups, CD8+ T cells were the most abundant in the LG (LG vs. MG vs. HG: 0.35 ± 0.15 vs. 0.27 ± 0.10 vs. 0.09 ± 0.02, P = 0.003), whereas CD68 macrophages were the most abundant in the HG (LG vs. MG vs. HG: 0.38 ± 0.09 vs. 0.64 ± 0.17 vs. 0.98 ± 0.19, P = 0.03) ( Figure 9A ).
PMC11502962
Gastrointestinal stromal tumors regulate macrophage M2 polarization through the MIF/CXCR4 axis to immune escape.
The expression of CD206 in the HG was the highest among the three groups (LG vs. MG vs. HG: 0.04 ± 0.01 vs. 0.07 ± 0.02 vs. 0.15 ± 0.03, P < 0.001).
PMC11502962
Gastrointestinal stromal tumors regulate macrophage M2 polarization through the MIF/CXCR4 axis to immune escape.
Such a phenomenon was also found in MIF expression and CXCR4 expression.
PMC11502962
Gastrointestinal stromal tumors regulate macrophage M2 polarization through the MIF/CXCR4 axis to immune escape.
Namely, among the three groups, the expression levels of MIF and CXCR4 were the highest in the HG (LG vs. MG vs. HG: 0.43 ± 0.24 vs. 0.90 ± 0.68 vs. 1.64 ± 0.53, P < 0.001; LG vs. MG vs. HG: 0.009 ± 0.003 vs. 0.70 ± 0.02 vs. 0.12 ± 0.03, P < 0.001) ( Figure 9B ).
PMC11502962
Gastrointestinal stromal tumors regulate macrophage M2 polarization through the MIF/CXCR4 axis to immune escape.
Summarily, CD8, CD68, CD206, MIF, and CXCR4 expression are related with tumor progression.
PMC11502962
Gastrointestinal stromal tumors regulate macrophage M2 polarization through the MIF/CXCR4 axis to immune escape.
Immunohistochemical characterization of CD8, CD68, MIF, CD206 and CXCR4 in GIST samples. (
PMC11502962
Gastrointestinal stromal tumors regulate macrophage M2 polarization through the MIF/CXCR4 axis to immune escape.
A) Immunofluorescence showed that co-expression of CD68 and CXCR4 in GIST sample. (
PMC11502962
Gastrointestinal stromal tumors regulate macrophage M2 polarization through the MIF/CXCR4 axis to immune escape.
B) Immunofluorescence showed that MIF expression is present both inside and outside GIST cells. (
PMC11502962
Gastrointestinal stromal tumors regulate macrophage M2 polarization through the MIF/CXCR4 axis to immune escape.
A) (A) There were differences in CD8+T cell infiltration among different groups (0.35 ± 0.15 vs 0.27 ± 0.10 vs 0.09 ± 0.02, P=0.003); (B) There were differences in the infiltration of CD68+macrophage cells among different groups (0.38 ± 0.09 vs 0.64 ± 0.17 vs 0.98 ± 0.19, P=0.03). (
PMC11502962
Gastrointestinal stromal tumors regulate macrophage M2 polarization through the MIF/CXCR4 axis to immune escape.
B) (A) As the risk increases, the expression of CXCR4 gradually increases, and the difference is statistically significant (0.43 ± 0.24 vs 0.90 ± 0.68 vs 1.64 ± 0.53, P<0.001); (B) As the risk increases, the expression of MIF gradually increases, and the difference is statistically significant (0.009 ± 0.003 vs 0.70 ± 0.02 vs 0.12 ± 0.03, P<0.001); (C) As the risk increases, the expression of CD206 gradually increases, and the difference is statistically significant (0.04 ± 0.01 vs 0.07 ± 0.0.02 vs 0.15 ± 0.03, P<0.001); The statistical method is non-parametric test, n=80, *P<0.05; **P<0.01.
PMC11502962
Gastrointestinal stromal tumors regulate macrophage M2 polarization through the MIF/CXCR4 axis to immune escape.
Previous data have shown high expression of MIF in GIST tissues.
PMC11502962
Gastrointestinal stromal tumors regulate macrophage M2 polarization through the MIF/CXCR4 axis to immune escape.
To determine whether GIST-882 cell line secretes MIF, we performed an ELISA trial.
PMC11502962
Gastrointestinal stromal tumors regulate macrophage M2 polarization through the MIF/CXCR4 axis to immune escape.
As expected, GIST-882 cell line secreted MIF, and MIF gradually increased with time.
PMC11502962
Gastrointestinal stromal tumors regulate macrophage M2 polarization through the MIF/CXCR4 axis to immune escape.
When we administered ISO-1 (MIF inhibitor) to the GIST-882 cell line, secretion of MIF decreased ( Figure 10 ). (
PMC11502962
Gastrointestinal stromal tumors regulate macrophage M2 polarization through the MIF/CXCR4 axis to immune escape.
A) GIST882 cells could express CD117; (B) GIST-882 cells could secrete MIF and MIF increased gradually along with the time.
PMC11502962
Gastrointestinal stromal tumors regulate macrophage M2 polarization through the MIF/CXCR4 axis to immune escape.
ISO-1 could inhibit the secretion of MIF.
PMC11502962
Gastrointestinal stromal tumors regulate macrophage M2 polarization through the MIF/CXCR4 axis to immune escape.
To explore the effect of GIST-882 cell line on macrophages in vitro, the cell supernatant was collected as conditioned medium (CM), cultured to M0 macrophages.
PMC11502962
Gastrointestinal stromal tumors regulate macrophage M2 polarization through the MIF/CXCR4 axis to immune escape.
Compared with the control group, M2 macrophages increased in the GIST882 CM group.
PMC11502962
Gastrointestinal stromal tumors regulate macrophage M2 polarization through the MIF/CXCR4 axis to immune escape.
However, when we administered ISO-1, M2 macrophages decreased.
PMC11502962
Gastrointestinal stromal tumors regulate macrophage M2 polarization through the MIF/CXCR4 axis to immune escape.
The difference between the two groups suggested that MIF was a factor to modulate M2 polarization of macrophages.
PMC11502962
Gastrointestinal stromal tumors regulate macrophage M2 polarization through the MIF/CXCR4 axis to immune escape.
Interestingly, when we administered WZ811 (CXCR4 antagonist), M2 macrophages also decreased ( Figures 11A, B ). (
PMC11502962
Gastrointestinal stromal tumors regulate macrophage M2 polarization through the MIF/CXCR4 axis to immune escape.
A) (A) GIST882 CM group; (B) GIST882 CM+ISO-1 group; Ctrl group vs GIST882 CM group, 1.6% vs 27.3%, P=0.000; GIST882 CM group vs GIST882 CM+ISO-1 group,27.3% vs 11.9%, P=0.006; ISO-1:MIF inhibitor; The statistical method is chi square test, **:P<0.01. (
PMC11502962
Gastrointestinal stromal tumors regulate macrophage M2 polarization through the MIF/CXCR4 axis to immune escape.
B) (A) GIST882CM group; (B) GIST882CM+WZ811 group.
PMC11502962
Gastrointestinal stromal tumors regulate macrophage M2 polarization through the MIF/CXCR4 axis to immune escape.
Ctrl vs GIST882CM group:1.6% vs 24.8%, P=0.000; GIST882CM group vs GIST882CM+WZ811group:24.8% vs 9.3%, P=0.004; WZ811:CXCR4 antagonists; The statistical method is chi square test, **:P<0.01.
PMC11502962
Gastrointestinal stromal tumors regulate macrophage M2 polarization through the MIF/CXCR4 axis to immune escape.
To further confirm the polarization of M2 macrophages, IL-10 mRNA and Arginase-1 mRNA were detected.
PMC11502962
Gastrointestinal stromal tumors regulate macrophage M2 polarization through the MIF/CXCR4 axis to immune escape.
The expression levels of IL-10 mRNA and Arginase-1 mRNA were in concordance with the results of flow cytometry, and were the highest in the GIST882 CM group ( Figure 12 ). (
PMC11502962
Gastrointestinal stromal tumors regulate macrophage M2 polarization through the MIF/CXCR4 axis to immune escape.
A) Ctrl vs GIST882CM vs GIST882CM +ISO-1 vs GIST882CM +WZ811:1.17 ± 0.43 vs 5.40 ± 1.21 vs 1.17 ± 0.23 vs 1.57 ± 0.57; (B) Ctrl vs GIST882CM vs GIST882CM +ISO-1 vs GIST882CM +WZ811:1.05 ± 0.18 vs 1.83 ± 0.18 vs 0.84 ± 0.30 vs 0.80 ± 0.17; ISO-1: MIF inhibitor; WZ811: CXCR4 antagonists; The statistical method is T-test, mean ± SEM, n=3, *P<0.05; **P<0.01.
PMC11502962
Gastrointestinal stromal tumors regulate macrophage M2 polarization through the MIF/CXCR4 axis to immune escape.
The incidence of GIST is 1.1 per 100,000, and accounts for 80% of all gastrointestinal sarcomas (22, 23).
PMC11502962
Gastrointestinal stromal tumors regulate macrophage M2 polarization through the MIF/CXCR4 axis to immune escape.
The most common sites for GIST are the stomach (60%) and the small intestine (30%) (2, 24).
PMC11502962
Gastrointestinal stromal tumors regulate macrophage M2 polarization through the MIF/CXCR4 axis to immune escape.
Given that mutations in KIT or PDGFRA have been identified, the treatment strategy for GIST is targeted therapy.
PMC11502962
Gastrointestinal stromal tumors regulate macrophage M2 polarization through the MIF/CXCR4 axis to immune escape.
Imatinib, sunitinib, regorafenib, and ripretinib have been approved for the treatment of GIST.
PMC11502962
Gastrointestinal stromal tumors regulate macrophage M2 polarization through the MIF/CXCR4 axis to immune escape.
Imatinib, the first-line system therapy, achieves an excellent disease control in 80% of patients (25).
PMC11502962
Gastrointestinal stromal tumors regulate macrophage M2 polarization through the MIF/CXCR4 axis to immune escape.
However, drug resistance is the most challenging clinical problem.
PMC11502962
Gastrointestinal stromal tumors regulate macrophage M2 polarization through the MIF/CXCR4 axis to immune escape.
As the new era of immunotherapy has arrived, the microenvironment of GIST and the roles of infiltrating cells in tumor surveillance and tumor progression should be clarified.
PMC11502962
Gastrointestinal stromal tumors regulate macrophage M2 polarization through the MIF/CXCR4 axis to immune escape.
CD3 T cells and macrophages have been found as the most abundant tumor-infiltrating immune cells in GIST (11, 12).
PMC11502962
Gastrointestinal stromal tumors regulate macrophage M2 polarization through the MIF/CXCR4 axis to immune escape.
Our results revealed that CD8 T cells and macrophages were the most abundant tumor-infiltrating immune cells.
PMC11502962
Gastrointestinal stromal tumors regulate macrophage M2 polarization through the MIF/CXCR4 axis to immune escape.
We also analyzed the differences among LG, MG, and HG.
PMC11502962
Gastrointestinal stromal tumors regulate macrophage M2 polarization through the MIF/CXCR4 axis to immune escape.
The results showed that macrophages were increased and CD8 T cells were exhausted with tumor progression, which is similar to other studies (11, 18).
PMC11502962
Gastrointestinal stromal tumors regulate macrophage M2 polarization through the MIF/CXCR4 axis to immune escape.
High infiltration of macrophages predicts poor prognosis in multiple types of tumors and is considered the reason of suppressed antitumor inflammatory setting (26–28).
PMC11502962
Gastrointestinal stromal tumors regulate macrophage M2 polarization through the MIF/CXCR4 axis to immune escape.
PD-1 expression by tumor-associated macrophages has been linked to inhibition of phagocytosis and immunity (29).
PMC11502962
Gastrointestinal stromal tumors regulate macrophage M2 polarization through the MIF/CXCR4 axis to immune escape.
The M1/M2 polarization states of macrophages play an important role in tumor progression (30).
PMC11502962
Gastrointestinal stromal tumors regulate macrophage M2 polarization through the MIF/CXCR4 axis to immune escape.
The inflammatory M1 state and protumor M2 state originate from different environmental stimuli (31).
PMC11502962
Gastrointestinal stromal tumors regulate macrophage M2 polarization through the MIF/CXCR4 axis to immune escape.
However, PD-1 expression has been found in M2-state tumor-associated macrophages (29).
PMC11502962
Gastrointestinal stromal tumors regulate macrophage M2 polarization through the MIF/CXCR4 axis to immune escape.
This discovery could explain the promotion of tumor progression by M2 macrophages.
PMC11502962
Gastrointestinal stromal tumors regulate macrophage M2 polarization through the MIF/CXCR4 axis to immune escape.
To clarify the polarization of macrophages in GIST, CD206 expression was examined.
PMC11502962
Gastrointestinal stromal tumors regulate macrophage M2 polarization through the MIF/CXCR4 axis to immune escape.
We showed that CD206 expression was the highest in the HG.
PMC11502962
Gastrointestinal stromal tumors regulate macrophage M2 polarization through the MIF/CXCR4 axis to immune escape.
However, the reason for the increase in tumor-infiltrating M2 macrophages in the high-risk GIST was not clear.
PMC11502962
Gastrointestinal stromal tumors regulate macrophage M2 polarization through the MIF/CXCR4 axis to immune escape.
So, we performed a CellChat analysis to clarify the crosstalk types between tumor cells and macrophages based on single-cell RNA sequencing data (32).
PMC11502962
Gastrointestinal stromal tumors regulate macrophage M2 polarization through the MIF/CXCR4 axis to immune escape.
Through CellChat, we quantitatively inferred and analyzed intercellular communication networks.
PMC11502962
Gastrointestinal stromal tumors regulate macrophage M2 polarization through the MIF/CXCR4 axis to immune escape.
The CellChat results showed that the MIF/CXCR4 axis was the main crosstalk type between tumor cells and macrophages.
PMC11502962
Gastrointestinal stromal tumors regulate macrophage M2 polarization through the MIF/CXCR4 axis to immune escape.
High expression of MIF has been found in many tumor tissues, such as breast cancer, lung cancer, and melanoma (33–35).
PMC11502962
Gastrointestinal stromal tumors regulate macrophage M2 polarization through the MIF/CXCR4 axis to immune escape.
It has also been revealed that high expression of MIF is closely related to tumor progression and metastasis (36).
PMC11502962
Gastrointestinal stromal tumors regulate macrophage M2 polarization through the MIF/CXCR4 axis to immune escape.
MIF could act on corresponding cells in autocrine or paracrine manner, resulting in changes in physiological functions.
PMC11502962
Gastrointestinal stromal tumors regulate macrophage M2 polarization through the MIF/CXCR4 axis to immune escape.
Currently, four receptors for MIF have been discovered, namely CD74, CXCR2, CXCR4, and CXCR7 (37–40).
PMC11502962
Gastrointestinal stromal tumors regulate macrophage M2 polarization through the MIF/CXCR4 axis to immune escape.
The MIF/CXCR4 axis has been found to contribute to cell survival, drug resistance, and tumor metastasis in multiple types of tumors (41–43).
PMC11502962
Gastrointestinal stromal tumors regulate macrophage M2 polarization through the MIF/CXCR4 axis to immune escape.
In ELISA trial, we found that GIST882 cells were able to secrete MIF, and immunohistochemical expression of MIF and CXCR4 was related to the recurrence risk.
PMC11502962
Gastrointestinal stromal tumors regulate macrophage M2 polarization through the MIF/CXCR4 axis to immune escape.
These results suggest that the MIF/CXCR4 axis could play a key role in GIST progression.
PMC11502962
Gastrointestinal stromal tumors regulate macrophage M2 polarization through the MIF/CXCR4 axis to immune escape.
In vitro, we found that the MIF/CXCR4 axis contributed to M2 polarization of macrophages.
PMC11502962
Gastrointestinal stromal tumors regulate macrophage M2 polarization through the MIF/CXCR4 axis to immune escape.
The expression levels of MIF and CXCR4 have been identified as adverse prognostic factors in multiple types of tumors (43–45).
PMC11502962
Gastrointestinal stromal tumors regulate macrophage M2 polarization through the MIF/CXCR4 axis to immune escape.
The MIF/CXCR4 axis could contribute to drug resistance in tumor invasion and metastasis (41, 43).
PMC11502962
Gastrointestinal stromal tumors regulate macrophage M2 polarization through the MIF/CXCR4 axis to immune escape.
However, the mechanism of the MIF/CXCR4 axis in this process is unclear.
PMC11502962
Gastrointestinal stromal tumors regulate macrophage M2 polarization through the MIF/CXCR4 axis to immune escape.
Our results provide an idea to explain this phenomenon and stimulate further research.
PMC11502962
Gastrointestinal stromal tumors regulate macrophage M2 polarization through the MIF/CXCR4 axis to immune escape.
In conclusion, macrophages are the most abundant infiltrating cells in GIST.
PMC11502962
Gastrointestinal stromal tumors regulate macrophage M2 polarization through the MIF/CXCR4 axis to immune escape.
The MIF/CXCR4 axis is the most ligand–receptor interaction between macrophages and tumor cells.
PMC11502962
Gastrointestinal stromal tumors regulate macrophage M2 polarization through the MIF/CXCR4 axis to immune escape.
GIST cells can regulate macrophage M2 polarization through the MIF/CXCR4 axis to form an immunosuppressive microenvironment.
PMC11641291
Gliotic Response and Reprogramming Potential of Human Müller Cell Line MIO-M1 Exposed to High Glucose and Glucose Fluctuations.
Retinal neurodegeneration (RN), an early marker of diabetic retinopathy (DR), is closely associated with Müller glia cells (MGs) in diabetic subjects.
PMC11641291
Gliotic Response and Reprogramming Potential of Human Müller Cell Line MIO-M1 Exposed to High Glucose and Glucose Fluctuations.
MGs play a pivotal role in maintaining retinal homeostasis, integrity, and metabolic support and respond to diabetic stress.
PMC11641291
Gliotic Response and Reprogramming Potential of Human Müller Cell Line MIO-M1 Exposed to High Glucose and Glucose Fluctuations.
In lower vertebrates, MGs have a strong regenerative response and can completely repair the retina after injuries.
PMC11641291
Gliotic Response and Reprogramming Potential of Human Müller Cell Line MIO-M1 Exposed to High Glucose and Glucose Fluctuations.
However, this ability diminishes as organisms become more complex.
PMC11641291
Gliotic Response and Reprogramming Potential of Human Müller Cell Line MIO-M1 Exposed to High Glucose and Glucose Fluctuations.
The aim of this study was to investigate the gliotic response and reprogramming potential of the human Müller cell line MIO-M1 cultured in normoglycemic (5 mM glucose, NG) and hyperglycemic (25 mM glucose, HG) conditions and then exposed to sustained high-glucose and glucose fluctuation (GF) treatments to mimic the human diabetic conditions.
PMC11641291
Gliotic Response and Reprogramming Potential of Human Müller Cell Line MIO-M1 Exposed to High Glucose and Glucose Fluctuations.
The results showed that NG MIO-M1 cells exhibited a dynamic activation to sustained high-glucose and GF treatments by increasing GFAP and Vimentin expression together, indicative of gliotic response.
PMC11641291
Gliotic Response and Reprogramming Potential of Human Müller Cell Line MIO-M1 Exposed to High Glucose and Glucose Fluctuations.
Increased expression of SHH and SOX2 were also observed, foreshadowing reprogramming potential.
PMC11641291
Gliotic Response and Reprogramming Potential of Human Müller Cell Line MIO-M1 Exposed to High Glucose and Glucose Fluctuations.
Conversely, HG MIO-M1 cells showed increased levels of the indexes reported above and adaptation/desensitization to sustained high-glucose and GF treatments.
PMC11641291
Gliotic Response and Reprogramming Potential of Human Müller Cell Line MIO-M1 Exposed to High Glucose and Glucose Fluctuations.
These findings indicate that MIO-M1 cells exhibit a differential response under various glucose treatments, which is dependent on the metabolic environment.
PMC11641291
Gliotic Response and Reprogramming Potential of Human Müller Cell Line MIO-M1 Exposed to High Glucose and Glucose Fluctuations.
The in vitro model used in this study, based on a well-established cell line, enables the exploration of how these responses occur in a controlled, reproducible system and the identification of strategies to promote neurogenesis over neurodegeneration.
PMC11641291
Gliotic Response and Reprogramming Potential of Human Müller Cell Line MIO-M1 Exposed to High Glucose and Glucose Fluctuations.
These findings contribute to the understanding of MGs responses under diabetic conditions, which may have implications for future therapeutic approaches to diabetes-associated retinal neurodegeneration.
PMC11641291
Gliotic Response and Reprogramming Potential of Human Müller Cell Line MIO-M1 Exposed to High Glucose and Glucose Fluctuations.
Diabetic retinopathy (DR) is the most common and sever microvascular complication of diabetes mellitus (DM), accounting for the majority of vision damage to the retina and blindness in adults .
PMC11641291
Gliotic Response and Reprogramming Potential of Human Müller Cell Line MIO-M1 Exposed to High Glucose and Glucose Fluctuations.
In recent years, the concept of DR as a microvascular disease has evolved, as it is now recognized as a more complex diabetic complication in which retinal neurodegeneration (RN) plays a significant role .
PMC11641291
Gliotic Response and Reprogramming Potential of Human Müller Cell Line MIO-M1 Exposed to High Glucose and Glucose Fluctuations.
In this contest, RN has recently been considered as an early marker of DR, since it seems to precede vascular damage .
PMC11641291
Gliotic Response and Reprogramming Potential of Human Müller Cell Line MIO-M1 Exposed to High Glucose and Glucose Fluctuations.
The neurovascular unit (NVU) in the retina refers to the functional coupling and interdependency of neurons (e.g., ganglion cells, amacrine cells, horizontal and bipolar cells), glia (e.g., Müller cells and astrocytes), immune cells (e.g., microglia and perivascular macrophages), and highly specialized vascular cells (e.g., endothelial cells and pericytes) .
PMC11641291
Gliotic Response and Reprogramming Potential of Human Müller Cell Line MIO-M1 Exposed to High Glucose and Glucose Fluctuations.
The impairment of the NVU represents a primary event in the pathogenesis of DR and is characterized by RN and early microvascular alterations.