Cell-cell communication in diabetic retinopathy

Roy, Sayon; Kim, Dongjoon; Lim, Remington

doi:10.1016/j.visres.2017.04.014

Cited by 40 publications

(24 citation statements)

References 93 publications

(69 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…As described previously physical contact between pericytes and endothelial cells is required for activation of TGF-β and deficiency of TGF-β signaling impairs vessel maturity and increases permeability ( 114 , 115 ). Additionally, ANG-1 released by pericytes has an important role in maintaining quiescence of the endothelial layer and reducing the permeability of the vessel.…”

Section: Dysfunctional Multicellular Interactions In Diseasementioning

confidence: 75%

It Takes Two: Endothelial-Perivascular Cell Cross-Talk in Vascular Development and Disease

Sweeney

Földes

2018

Front. Cardiovasc. Med.

143

View full text Add to dashboard Cite

The formation of new blood vessels is a crucial step in the development of any new tissue both during embryogenesis and in vitro models as without sufficient perfusion the tissue will be unable to grow beyond the size where nutrition and oxygenation can be managed by diffusion alone. Endothelial cells are the primary building block of blood vessels and are capable of forming tube like structures independently however they are unable to independently form functional vasculature which is capable of conducting blood flow. This requires support from other structures including supporting perivascular cells and the extracellular matrix. The crosstalk between endothelial cells and perivascular cells is vital in regulating vasculogenesis and angiogenesis and the consequences when this is disrupted can be seen in a variety of congenital and acquired disease states. This review details the mechanisms of vasculogenesis in vivo during embryogenesis and compares this to currently employed in vitro techniques. It also highlights clinical consequences of defects in the endothelial cell—pericyte cross-talk and highlights therapies which are being developed to target this pathway. Improving the understanding of the intricacies of endothelial—pericyte signaling will inform pathophysiology of multiple vascular diseases and allow the development of effective in vitro models to guide drug development and assist with approaches in tissue engineering to develop functional vasculature for regenerative medicine applications.

show abstract

Section: Dysfunctional Multicellular Interactions In Diseasementioning

confidence: 75%

It Takes Two: Endothelial-Perivascular Cell Cross-Talk in Vascular Development and Disease

Sweeney

Földes

2018

Front. Cardiovasc. Med.

143

View full text Add to dashboard Cite

show abstract

“…In CKD, diabetic nephropathy accounts for approximately 50% of patients presenting with end-stage renal failure [1]. Hyperglycemia and downstream changes in connexin expression are critical in the development and progression of secondary micro-vascular complications, [12][13][14][15] with glucose decreasing gap junction conductance and disrupting cellular homeostasis in a variety of cell types [16][17][18][19]. Evidence that connexin expression is linked to renal damage in CKD [9,11,12,[20][21][22][23][24], suggests that they represent a viable therapeutic target for treatment of the disease.…”

Section: Introductionmentioning

confidence: 99%

Blocking Connexin-43 mediated hemichannel activity protects against early tubular injury in experimental chronic kidney disease

Price¹,

Chadjichristos²,

Kavvadas³

et al. 2020

Cell Commun Signal

View full text Add to dashboard Cite

Background: Tubulointerstitial fibrosis represents the key underlying pathology of Chronic Kidney Disease (CKD), yet treatment options remain limited. In this study, we investigated the role of connexin43 (Cx43) hemichannelmediated adenosine triphosphate (ATP) release in purinergic-mediated disassembly of adherens and tight junction complexes in early tubular injury. Methods: Human primary proximal tubule epithelial cells (hPTECs) and clonal tubular epithelial cells (HK2) were treated with Transforming Growth Factor Beta1 (TGF-β1) ± apyrase, or ATPγS for 48 h. For inhibitor studies, cells were co-incubated with Cx43 mimetic Peptide 5, or purinergic receptor antagonists Suramin, A438079 or A804598. Immunoblotting, single-cell force spectroscopy and trans-epithelial electrical resistance assessed protein expression, cell-cell adhesion and paracellular permeability. Carboxyfluorescein uptake and biosensing measured hemichannel activity and real-time ATP release, whilst a heterozygous Cx43 +/− mouse model with unilateral ureteral obstruction (UUO) assessed the role of Cx43 in vivo. Results: Immunohistochemistry of biopsy material from patients with diabetic nephropathy confirmed increased expression of purinergic receptor P2X7. TGF-β1 increased Cx43 mediated hemichannel activity and ATP release in hPTECs and HK2 cells. The cytokine reduced maximum unbinding forces and reduced cell-cell adhesion, which translated to increased paracellular permeability. Changes were reversed when cells were co-incubated with either Peptide 5 or P2-purinoceptor inhibitors. Cx43 +/− mice did not exhibit protein changes associated with early tubular injury in a UUO model of fibrosis. Conclusion: Data suggest that Cx43 mediated ATP release represents an initial trigger in early tubular injury via its actions on the adherens and tight junction complex. Since Cx43 is highly expressed in nephropathy, it represents a novel target for intervention of tubulointerstitial fibrosis in CKD.

show abstract

“…In mouse liver, hepatocytes predominantly express connexin32 (Cx32), and to a less extent connexin26 (Cx26) in the gap junctional plaque [4,5]. Most tissues express more than one connexin type that can be regulated by hormones, growth factors and proinflammatory mediators, thus ensuring a fine-tuned regulation of GJIC [6,7].…”

Section: Introductionmentioning

confidence: 99%

Gadolinium Chloride Restores the Function of the Gap Junctional Intercellular Communication between Hepatocytes in a Liver Injury

Yang

Dong

Tian

et al. 2019

IJMS

View full text Add to dashboard Cite

Background: Gadolinium chloride (GdCl3) has been reported to attenuate liver injury caused by a variety of toxicants. Gap junctional intercellular communication (GJIC) is thought to be essential in controlling liver homeostasis and pathology. Here we evaluate the effects of GdCl3 on functional GJIC and connexin expression in mouse models and primary hepatocytes. Methods: Mice were administered GdCl3 intraperitoneally the day before a carbon tetrachloride (CCl4) injection or bile duct ligation (BDL) operation. Primary hepatocytes were treated with CCl4 or lipopolysaccharides (LPS), with or without GdCl3. A scrape loading/dye transfer assay was performed to assess the GJIC function. The expression of connexins was examined by real-time reverse transcription polymerase chain reaction (RT-PCR), western blot and immunofluorescent staining. Results: CCl4 treatment or the BDL operation led to the dysfunction of GJIC and a down-regulation of Cx32 and Cx26 in injured liver. GdCl3 administration restored GJIC function between hepatocytes by facilitating the transfer of fluorescent dye from one cell into adjacent cells via GJIC, and markedly prevented the decrease of Cx32 and Cx26 in injured liver. In primary hepatocytes, CCl4 or LPS treatment induced an obvious decline of Cx32 and Cx26, whereas GdCl3 pretreatment prevented the down-regulation of connexins. In vivo GdCl3 protected hepatocytes and attenuated the liver inflammation and fibrosis in liver injury mouse models. Conclusion: GdCl3 administration protects functional GJIC between hepatocytes, and prevents the decrease of connexin proteins at mRNA and protein levels during liver injury, leading to the alleviation of chronic liver injury.

show abstract

Cell-cell communication in diabetic retinopathy

Cited by 40 publications

References 93 publications

It Takes Two: Endothelial-Perivascular Cell Cross-Talk in Vascular Development and Disease

It Takes Two: Endothelial-Perivascular Cell Cross-Talk in Vascular Development and Disease

Blocking Connexin-43 mediated hemichannel activity protects against early tubular injury in experimental chronic kidney disease

Gadolinium Chloride Restores the Function of the Gap Junctional Intercellular Communication between Hepatocytes in a Liver Injury

Contact Info

Product

Resources

About