Purinergic modulation of mesangial extracellular matrix production: Role in diabetic and other glomerular diseases

Solini, Anna; Iacobini, Carla; Ricci, C; Chiozzi, Paola; Amadio, Lorena; Pricci, Flavia; Mario, U. Di; Virgilio, Francesco Di; Pugliese, Giuseppe

doi:10.1111/j.1523-1755.2005.00152.x

Cited by 64 publications

(66 citation statements)

References 52 publications

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“…The first expression of P2X 7 R in renal disease was described in a rat model of diabetes and hypertension [60]. Moreover, Solini and colleagues [61] demonstrated the importance of P2X 7 R activation in TGF-β1 secretion and ECM production from mesangial cells. In addition, tubulo-interstitial damage and fibrosis induced after unilateral ureteral obstruction (UUO) are attenuated in the absence of P2X 7 R. Indeed, P2X 7 R (-/-) knockout UUO mice have a lower population of myofibroblasts, diminished collagen deposition, and decreased TGF-β1 expression in the renal interstitium compared to wildtype UUO mice [62].…”

Section: Renal Fibrosismentioning

confidence: 99%

The role of P2X7 receptors in tissue fibrosis: a brief review

Gentile

Natale

Lazzerini

et al. 2015

Purinergic Signalling

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Many previous studies have demonstrated that P2X 7 receptors (P2X 7 Rs) have a pleiotropic function in different pathological conditions and could represent a novel target for the treatment of a range of diseases. In particular, recent studies have explored the role of P2X 7 R in fibrosis, the pathological outcome of most chronic inflammatory diseases. The aim of this review is to discuss the biological features of P2X 7 R and summarize the current knowledge about the putative role of the P2X 7 R in triggering fibrosis in a wide spectrum of organs such as the lung, kidney, liver, pancreas, and heart.

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Section: Renal Fibrosismentioning

confidence: 99%

The role of P2X7 receptors in tissue fibrosis: a brief review

Gentile

Natale

Lazzerini

et al. 2015

Purinergic Signalling

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“…Increased ATP release induced by hyperglycaemia may contribute to mesangial extracellular matrix expansion that occurs in diabetes [346]. Increased expression of P2X7 receptors was shown in the streptozotocin diabetic rat model, mainly in podocytes but also in endothelial and mesangial cells [393].…”

Section: Diabetic Nephropathymentioning

confidence: 99%

Purinergic signalling in the kidney in health and disease

Burnstock

Evans

Bailey

2013

Purinergic Signalling

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The involvement of purinergic signalling in kidney physiology and pathophysiology is rapidly gaining recognition and this is a comprehensive review of early and recent publications in the field. Purinergic signalling involvement is described in several important intrarenal regulatory mechanisms, including tuboglomerular feedback, the autoregulatory response of the glomerular and extraglomerular microcirculation and the control of renin release. Furthermore, purinergic signalling influences water and electrolyte transport in all segments of the renal tubule. Reports about purine-and pyrimidine-mediated actions in diseases of the kidney, including polycystic kidney disease, nephritis, diabetes, hypertension and nephrotoxicant injury are covered and possible purinergic therapeutic strategies discussed.

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“…High glucose levels stimulate the release of ATP into the extracellular space from several tissues and cell types such as endothelial cells, blood vessels, mesangial cells, macrophages and beta cells [1][2][3][4][5]. The net pharmacological effects of extracellular ATP are difficult to predict since ATP by itself can stimulate P2Y 2 , P2Y 4 (in rodents), P2Y 11 and P2X 1 -P2X 7 receptors present on the cell surface [6].…”

Section: Introductionmentioning

confidence: 99%

ADP mediates inhibition of insulin secretion by activation of P2Y13 receptors in mice

et al. 2010

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Aims/hypotheses To investigate the effects of extracellular purines on insulin secretion from mouse pancreatic islets. Methods Mouse islets and beta cells were isolated and examined with mRNA real-time quantification, cAMP quantification and insulin and glucagon secretion. ATP release was measured in MIN6c4 cells. Insulin and glucagon secretion were measured in vivo after glucose injection. Results Enzymatic removal of extracellular ATP at low glucose levels increased the secretion of both insulin and glucagon, while at high glucose levels insulin secretion was reduced and glucagon secretion was stimulated, indicating an autocrine effect of purines. In MIN6c4 cells it was shown that glucose does induce release of ATP into the extracellular space. Quantitative real-time PCR demonstrated the expression of the ADP receptors P2Y 1 and P2Y 13 in both intact mouse pancreatic islets and isolated beta cells. The stable ADP analogue 2-MeSADP had no effect on insulin secretion. However, co-incubation with the P2Y 1 antagonist MRS2179 inhibited insulin secretion, while coincubation with the P2Y 13 antagonist MRS2211 stimulated insulin secretion, indicating that ADP acting via P2Y 1 stimulates insulin secretion, while signalling via P2Y 13 inhibits the secretion of insulin. P2Y 13 antagonism through MRS2211 per se increased the secretion of both insulin and glucagon at intermediate (8.3 mmol/l) and high (20 mmol/l) glucose levels, confirming an autocrine role for ADP. Administration of MRS2211 during glucose injection in vivo resulted in both increased secretion of insulin and reduced glucose levels. Conclusions/interpretation In conclusion, ADP acting on the P2Y 13 receptors inhibits insulin release. An antagonist to P2Y 13 increases insulin release and could be evaluated for the treatment of diabetes.

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Purinergic modulation of mesangial extracellular matrix production: Role in diabetic and other glomerular diseases

Abstract: These data indicate a role for eATP in regulating ECM production via TGF-beta and suggest that P2XRs and P2YRs differentially modulate this process. An increased ATP release induced by hyperglycemia might contribute to mesangial matrix expansion occurring in diabetes.

Cited by 64 publications

References 52 publications

The role of P2X7 receptors in tissue fibrosis: a brief review

The role of P2X7 receptors in tissue fibrosis: a brief review

Purinergic signalling in the kidney in health and disease

ADP mediates inhibition of insulin secretion by activation of P2Y13 receptors in mice

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