Mesangial Cells and Glomerular Inflammation: From the Pathogenesis to Novel Therapeutic Approaches

Gómez-Guerrero, Carmen; Hernández-Vargas, Purificación; López-Franco, Óscar; Ortiz-Muñoz, Guadalupe; Egido, Jesús

doi:10.2174/1568010054022169

Cited by 67 publications

(54 citation statements)

References 169 publications

(378 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…The mesangium occupies a central anatomical position in the glomerulus, located between the fenestrated endothelial lining of the capillary lumen and the glomerular basement membrane. This structure is involved in the pathology of all types of chronic, progressive kidney diseases (26). The mesangium is composed of mesangial cells embedded in the mesangial matrix, providing structural support to capillary loops and modulating glomerular filtration (27).…”

Section: Discussionmentioning

confidence: 99%

“…The mesangium is composed of mesangial cells embedded in the mesangial matrix, providing structural support to capillary loops and modulating glomerular filtration (27). Mesangial cell responses to pathological stimuli are associated with the main events of glomerular injury, leukocyte infiltration, cell proliferation and NF-κB and MCP-1 expression (26,28). The present study demonstrated that the number of TUNEL-positive mesangial cells was significantly increased under high glucose conditions and CHOP was simultaneously induced.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

C/EBP homologous protein induces mesangial cell apoptosis under hyperglycemia

Zhao

et al. 2012

Molecular Medicine Reports

View full text Add to dashboard Cite

Abstract. Diabetes mellitus is known to cause kidney impairment; however, the mechanism remains elusive. The aim of this study was to investigate the role of C/EBP homologous protein (CHOP), an important protein in endoplasmic reticulum stress-mediated mesangial cell apoptosis in hyperglycemia. Mesangial cells were cultured in normal (control group) and high glucose medium (high glucose group). TUNEL staining was performed to assess apoptotic cells in the groups. The expression of CHOP and caspase-3 was also assayed by immunohistochemistry and western blot analysis. Following 24 h culture in high glucose medium, TUNEL-positive cells were observed to be significantly increased (P<0.01). The expression of CHOP and caspase-3 in mesangial cells was also found to be significantly enhanced under high glucose conditions compared with the normal group (P<0.01). The results indicate that CHOP mediates apoptosis in mesangial cells under hyperglycemia and may play a role in the development of diabetic nephropathy.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

C/EBP homologous protein induces mesangial cell apoptosis under hyperglycemia

Zhao

et al. 2012

Molecular Medicine Reports

View full text Add to dashboard Cite

show abstract

“…Extracellular matrix accumulation in glomeruli contributes to the pathogenesis of glomerulosclerosis in fibrotic renal diseases (1)(2)(3)(4). Up-regulation of the renin-angiotensin system plays a key role in the initiation and the progression of glomerular injury via induction of extracellular matrix expansion in glomerular mesangial cells (MCs) 4 (4 -10).…”

mentioning

confidence: 99%

Nox4 NADPH Oxidase Mediates Peroxynitrite-dependent Uncoupling of Endothelial Nitric-oxide Synthase and Fibronectin Expression in Response to Angiotensin II

Lee¹,

Wauquier²,

Eid³

et al. 2013

Journal of Biological Chemistry

116

105

View full text Add to dashboard Cite

Background: Oxidative stress is critical for the fibrotic response of mesangial cells (MCs) to angiotensin II. Results: Nox4-and mitochondrial reactive oxygen species (ROS)-dependent endothelial nitric-oxide synthase (eNOS) uncoupling led to fibronectin accumulation in MCs stimulated by angiotensin II. Conclusion: The Nox4/mitochondrial ROS/eNOS pathway mediates angiotensin II-induced MC injury. Significance: Targeting Nox4 and mitochondrial ROS is a promising therapeutic approach.

show abstract

“…Cellular hypertrophy and extracellular matrix accumulation in glomeruli contributes to the pathogenesis of glomerulosclerosis in fibrotic renal diseases (1)(2)(3)(4)(5). The octapeptide hormone angiotensin II (Ang II) 2 is the dominant renin-angiotensin system effector (5)(6)(7) and is implicated in the pathogenesis of fibrosis of the glomerular microvascular bed.…”

mentioning

confidence: 99%

Nox4 NAD(P)H Oxidase Mediates Src-dependent Tyrosine Phosphorylation of PDK-1 in Response to Angiotensin II

Block

Eid

Griendling

et al. 2008

Journal of Biological Chemistry

125

133

View full text Add to dashboard Cite

Activation of glomerular mesangial cells (MCs) by angiotensin II (Ang II) leads to hypertrophy and extracellular matrix accumulation. Here, we demonstrate that, in MCs, Ang II induces an increase in PDK-1 (3-phosphoinositide-dependent protein kinase-1) kinase activity that required its phosphorylation on tyrosine 9 and 373/376. Introduction into the cells of PDK-1, mutated on these tyrosine residues or kinase-inactive, attenuates Ang II-induced hypertrophy and fibronectin accumulation. Ang II-mediated PDK-1 activation and tyrosine phosphorylation (total and on residues 9 and 373/376) are inhibited in cells transfected with small interfering RNA for Src, indicating that Src is upstream of PDK-1. In cells expressing oxidationresistant Src mutant C487A, Ang II-induced hypertrophy and fibronectin expression are prevented, suggesting that the pathway is redox-sensitive. Ang II also up-regulates Nox4 protein, and siNox4 abrogates the Ang II-induced increase in intracellular reactive oxygen species (ROS) generation. Small interfering RNA for Nox4 also inhibits Ang II-induced activation of Src and PDK-1 tyrosine phosphorylation (total and on residues 9 and 373/376), demonstrating that Nox4 functions upstream of Src and PDK-1. Importantly, inhibition of Nox4, Src, or PDK-1 prevents the stimulatory effect of Ang II on fibronectin accumulation and cell hypertrophy. This work provides the first evidence that Nox4-derived ROS are responsible for Ang II-induced PDK-1 tyrosine phosphorylation and activation through stimulation of Src. Importantly, this pathway contributes to Ang IIinduced MC hypertrophy and fibronectin accumulation. These data shed light on molecular processes underlying the oxidative signaling cascade engaged by Ang II and identify potential targets for intervention to prevent renal hypertrophy and fibrosis.Cellular hypertrophy and extracellular matrix accumulation in glomeruli contributes to the pathogenesis of glomerulosclerosis in fibrotic renal diseases (1-5). The octapeptide hormone angiotensin II (Ang II) 2 is the dominant renin-angiotensin system effector (5-7) and is implicated in the pathogenesis of fibrosis of the glomerular microvascular bed. Up-regulation of the renin-angiotensin system plays a key role in the initiation and the progression of glomerular injury via induction of hypertrophy and extracellular matrix expansion in glomerular mesangial cells (MCs) (6 -13).Ang II-induced oxidative stress has emerged as a critical pathogenic factor in the development of renal and vascular diseases (13-16). NAD(P)H oxidases of the Nox family are major sources of reactive oxygen species (ROS) in many nonphagocytic cells, including renal cells (17-21). The Nox proteins correspond to homologues of gp91 phox (or Nox2), the catalytic moiety found in phagocytes (17,18). Seven members of the Nox family have been identified in the human genome: Nox1 to -5 and the dual oxidases Duox1 and -2 (17, 18, 22). The isoform Nox4 (NAD(P)H oxidase 4) is abundant in the vascular system and kidney cortex (16, 17, 19 -22). We ...

show abstract

Mesangial Cells and Glomerular Inflammation: From the Pathogenesis to Novel Therapeutic Approaches

Cited by 67 publications

References 169 publications

C/EBP homologous protein induces mesangial cell apoptosis under hyperglycemia

C/EBP homologous protein induces mesangial cell apoptosis under hyperglycemia

Nox4 NADPH Oxidase Mediates Peroxynitrite-dependent Uncoupling of Endothelial Nitric-oxide Synthase and Fibronectin Expression in Response to Angiotensin II

Nox4 NAD(P)H Oxidase Mediates Src-dependent Tyrosine Phosphorylation of PDK-1 in Response to Angiotensin II

Contact Info

Product

Resources

About