CXCL10 suppression of hem- and lymph-angiogenesis in inflamed corneas through MMP13

Gao, Nan; Liu, Xiaowei; Wu, Jiayin; Li, Juan; Chen, Dong; Wu, Xinyi; Xiao, Xiao; Yu, Fu–Shin X.

doi:10.1007/s10456-017-9561-x

Cited by 33 publications

(29 citation statements)

References 60 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…3c). The different cell types can be identified with specific cell markers by immunostaining whole-mount preparations [101] of the aortic cultures (Fig. 3d–g).…”

Section: Aortic Ring Assaymentioning

confidence: 99%

Consensus guidelines for the use and interpretation of angiogenesis assays

et al. 2018

View full text Add to dashboard Cite

The formation of new blood vessels, or angiogenesis, is a complex process that plays important roles in growth and development, tissue and organ regeneration, as well as numerous pathological conditions. Angiogenesis undergoes multiple discrete steps that can be individually evaluated and quantified by a large number of bioassays. These independent assessments hold advantages but also have limitations. This article describes in vivo, ex vivo, and in vitro bioassays that are available for the evaluation of angiogenesis and highlights critical aspects that are relevant for their execution and proper interpretation. As such, this collaborative work is the first edition of consensus guidelines on angiogenesis bioassays to serve for current and future reference.

show abstract

“…3c). The different cell types can be identified with specific cell markers by immunostaining whole-mount preparations [101] of the aortic cultures (Fig. 3d–g).…”

Section: Aortic Ring Assaymentioning

confidence: 99%

Consensus guidelines for the use and interpretation of angiogenesis assays

et al. 2018

View full text Add to dashboard Cite

show abstract

“…These results may indicate that the angiostatic effect of the CXCR3 ligands is a CXCR3-dependent phenomenon, at least when chemokines are exogenously added. Moreover, in a murine model of Candida albicans uveitis, neutralization of CXCR3 increased angiogenesis in the cornea, indicating that murine CXCR3 in this model provides a negative feedback on vessel formation ( 181 ). A similar observation was made in vitro in cocultures of human pericytes and endothelial cells.…”

Section: Unprecedented Versatility Of Ifn-inducible Cxcr3 Ligands As mentioning

confidence: 99%

Overview of the Mechanisms that May Contribute to the Non-Redundant Activities of Interferon-Inducible CXC Chemokine Receptor 3 Ligands

et al. 2018

View full text Add to dashboard Cite

The inflammatory chemokines CXCL9, CXCL10, and CXCL11 are predominantly induced by interferon (IFN)-γ and share an exclusive chemokine receptor named CXC chemokine receptor 3 (CXCR3). With a prototype function of directing temporal and spatial migration of activated T cells and natural killer cells, and inhibitory effects on angiogenesis, these CXCR3 ligands have been implicated in infection, acute inflammation, autoinflammation and autoimmunity, as well as in cancer. Intense former research efforts led to recent and ongoing clinical trials using CXCR3 and CXCR3 ligand targeting molecules. Scientific evidence has claimed mutual redundancy, ligand dominance, collaboration or even antagonism, depending on the (patho)physiological context. Most research on their in vivo activity, however, illustrates that CXCL9, CXCL10, and CXCL11 each contribute to the activation and trafficking of CXCR3 expressing cells in a non-redundant manner. When looking into detail, one can unravel a multistep machinery behind final CXCR3 ligand functions. Not only can specific cell types secrete individual CXCR3 interacting chemokines in response to certain stimuli, but also the receptor and glycosaminoglycan interactions, major associated intracellular pathways and susceptibility to processing by particular enzymes, among others, seem ligand-specific. Here, we overview major aspects of the molecular properties and regulatory mechanisms of IFN-induced CXCR3 ligands, and propose that their in vivo non-redundancy is a reflection of the unprecedented degree of versatility that seems inherent to the IFN-related CXCR3 chemokine system.

show abstract

“…In such a context, a very recent study has demonstrated that levels of CXCL10 and CXCL11, two C-X-C chemokines exerting angiostatic effects through their receptor CXCR3-B [49], are strongly increased in the circulation of SSc patients from the earliest disease stages, and may represent good biomarkers of vascular damage progression [50]. Interestingly, both CXCL10 and CXCL11 have been reported to potently inhibit the lymphangiogenic process [51,52], making them very attractive candidates as possible mediators of SSc-related, disturbed lymphangiogenesis, and are worthy of future investigation.…”

Section: Discussionmentioning

confidence: 99%

Systemic Sclerosis Serum Significantly Impairs the Multi-Step Lymphangiogenic Process: In Vitro Evidence

Manetti

Romano

Rosa

et al. 2019

IJMS

View full text Add to dashboard Cite

In systemic sclerosis (SSc), the possible involvement of lymphatic microcirculation and lymphangiogenesis has traditionally been overshadowed by the greater emphasis placed on dysfunctional blood vascular system and angiogenesis. In the present in vitro study, we explore for the first time whether the SSc microenvironment may interfere with lymphangiogenesis, a complex, multi-step process in which lymphatic microvascular endothelial cells (LMVECs) sprout, migrate, and proliferate to generate new lymphatic capillaries. Normal human adult dermal LMVECs from three donors were treated with serum from SSc patients (n = 8), serum from healthy individuals (n = 8), or recombinant human vascular endothelial growth factor (VEGF)-C as a positive control for lymphangiogenesis. Cell proliferation, Boyden chamber Matrigel chemoinvasion, wound healing capacity, and lymphatic capillary morphogenesis on Geltrex were assayed. VEGF-C serum levels were measured by enzyme-linked immunosorbent assay. Gene and protein expression levels of the lymphangiogenic orchestrators VEGF receptor-3 (VEGFR-3)/Flt-4 and neuropilin-2 (NRP-2) were determined by real-time PCR and Western blotting, respectively. Conditioning with SSc serum significantly inhibited LMVEC proliferation, Matrigel invasion, and wound healing capacity with respect to healthy serum. The ability of LMVECs to form lymphatic tubes on Geltrex was also severely compromised in the presence of SSc serum. VEGF-C levels were comparable in SSc and healthy sera. Treatment with SSc serum resulted in a significant downregulation of both VEGFR-3/Flt-4 and NRP-2 mRNA and protein levels. In SSc, the pathologic environment severely hampers every lymphangiogenesis step, likely through the reduction of pro-lymphangiogenic VEGFR-3/NRP-2 co-receptor signaling. The impairment of the lymphangiogenic process opens a new scenario underlying SSc vascular pathophysiology, which is worth investigating further.

show abstract

CXCL10 suppression of hem- and lymph-angiogenesis in inflamed corneas through MMP13

Cited by 33 publications

References 60 publications

Consensus guidelines for the use and interpretation of angiogenesis assays

Consensus guidelines for the use and interpretation of angiogenesis assays

Overview of the Mechanisms that May Contribute to the Non-Redundant Activities of Interferon-Inducible CXC Chemokine Receptor 3 Ligands

Systemic Sclerosis Serum Significantly Impairs the Multi-Step Lymphangiogenic Process: In Vitro Evidence

Contact Info

Product

Resources

About