Human Podocytes Adhere to the KRGDS Motif of the α3α4α5 Collagen IV Network

Borza, Corina M.; Borza, Dorin-Bogdan; Pedchenko, Vadim; Saleem, Moin A.; Mathieson, Peter W.; Sado, Yoshikazu; Hudson, Heather M.; Pozzi, Ambra; Saus, Juan; Abrahamson, Dale R.; Zent, Roy; Hudson, Billy G.

doi:10.1681/asn.2007070793

Cited by 32 publications

(32 citation statements)

References 35 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…For analysis of pStat3 and total Stat3 in primary or immortalized mesangial cells, 5310 4 SDS-PAGE, transferred onto nitrocellulose, and then probed with anticollagen IV or anti-focal adhesion kinas (FAK) (Santa Cruz) followed by horseradish peroxidase-conjugated secondary antibodies. Collagen IV and b-actin or FAK as well as pStat3 and Stat3 bands were quantified by densitometry analysis; the collagen IV signal was expressed as a collagen IV/b-actin or collagen IV/FAK ratio, whereas the pStat3 levels were expressed as pStat3/Stat3 ratio.…”

Section: Western Blot Analysismentioning

confidence: 99%

“…4 We have shown that integrin a1b1 is a negative modulator of glomerular injury by showing that integrin a1-null mice develop more severe glomerulosclerosis after injury, which is characterized by excessive collagen IV deposition, ROS generation, and EGF receptor activation. 3,5 We also showed that integrin a1b1 negatively regulates EGF receptor activation, generation of profibrotic ROS, and consequent collagen levels in mesangial cells in vitro.…”

mentioning

confidence: 97%

“…3,4 Two injury models were used in the genetic approach. In the first model, BALB/c mice were injected with adriamycin, which induces proteinuria, focal segmental glomerulosclerosis, and tubulointerstitial fibrosis because of ROS generation 3 (reviewed in ref.…”

mentioning

confidence: 99%

See 2 more Smart Citations

Inhibition of Integrin α2β1 Ameliorates Glomerular Injury

Borza

Su²,

Chen³

et al. 2012

Journal of the American Society of Nephrology

Self Cite

View full text Add to dashboard Cite

Mesangial cells and podocytes express integrins a1b1 and a2b1, which are the two major collagen receptors that regulate multiple cellular functions, including extracellular matrix homeostasis. Integrin a1b1 protects from glomerular injury by negatively regulating collagen production, but the role of integrin a2b1 in renal injury is unclear. Here, we subjected wild-type and integrin a2-null mice to injury with adriamycin or partial renal ablation. In both of these models, integrin a2-null mice developed significantly less proteinuria and glomerulosclerosis. In addition, selective pharmacological inhibition of integrin a2b1 significantly reduced adriamycin-induced proteinuria, glomerular injury, and collagen deposition in wildtype mice. This inhibitor significantly reduced collagen synthesis in wild-type, but not integrin a2-null, mesangial cells in vitro, demonstrating that its effects are integrin a2b1-dependent. Taken together, these results indicate that integrin a2b1 contributes to glomerular injury by positively regulating collagen synthesis and suggest that its inhibition may be a promising strategy to reduce glomerular injury and proteinuria. The most common cause of end stage kidney disease is glomerulosclerosis, which is characterized by excessive collagen deposition in the glomerulus. Although numerous disease processes can initiate glomerular injury, they all result in abnormal glomerular collagen homeostasis with progression. Glomerular collagen turnover is regulated by multiple factors, including growth factors and profibrotic reactive oxygen species (ROSs) as well as cell extracellular matrix interactions mediated by the matrix receptors integrins (reviewed in ref. 1). Of these factors, the mechanisms by which integrins regulate glomerulosclerosis are the most poorly understood.Integrins consist of two noncovalently associated a-and b-subunits that combine to form 24 different heterodimers in mammals (reviewed in ref.2). The integrin extracellular domains contain the ligand binding site and confer ligand specificity, whereas the cytoplasmic domain interacts with the cytoskeleton and regulates cell signaling. Integrins control critical cell functions, including proliferation, survival, migration, and matrix homeostasis (reviewed in refs. 1 and 2). Thus, it is not surprising that integrins regulate tissue responses to injury in whole organisms.The best-studied integrin in the context of glomerular injury is the major collagen IV receptor, integrin a1b1, which is expressed by mesangial cells 3 and podocytes. 4 We have shown that integrin

show abstract

Section: Western Blot Analysismentioning

confidence: 99%

mentioning

confidence: 97%

See 1 more Smart Citation

Inhibition of Integrin α2β1 Ameliorates Glomerular Injury

Borza

Su²,

Chen³

et al. 2012

Journal of the American Society of Nephrology

Self Cite

View full text Add to dashboard Cite

show abstract

“…19 Alternatively, anti-a3NC1 antibodies in complex with a3NC1 antigen may act as surrogate antipodocyte antibodies, because a3NC1-containing ICs bind to podocytes. 20 After four immunizations with a3NC1 monomers, B6 mice and DBA/1 mice eventually develop crescentic GN by 26 and 10 weeks, respectively. 10,14 The combination of subepithelial ICs and crescentic anti-GBM antibody GN was most recently described in a series of eight patients with circulating anti-a3NC1 autoantibodies but undetectable anti-PLA2R autoantibodies.…”

mentioning

confidence: 99%

Neonatal Fc Receptor Promotes Immune Complex–Mediated Glomerular Disease

Olaru

Luo

Suleiman³

et al. 2014

Journal of the American Society of Nephrology

Self Cite

View full text Add to dashboard Cite

The neonatal Fc receptor (FcRn) is a major regulator of IgG and albumin homeostasis systemically and in the kidneys. We investigated the role of FcRn in the development of immune complex-mediated glomerular disease in mice. C57Bl/6 mice immunized with the noncollagenous domain of the a3 chain of type IV collagen (a3NC1) developed albuminuria associated with granular capillary loop deposition of exogenous antigen, mouse IgG, C3 and C5b-9, and podocyte injury. High-resolution imaging showed abundant IgG deposition in the expanded glomerular basement membrane, especially in regions corresponding to subepithelial electron dense deposits. FcRn-null and -humanized mice immunized with a3NC1 developed no albuminuria and had lower levels of serum IgG anti-a3NC1 antibodies and reduced glomerular deposition of IgG, antigen, and complement. Our results show that FcRn promotes the formation of subepithelial immune complexes and subsequent glomerular pathology leading to proteinuria, potentially by maintaining higher serum levels of pathogenic IgG antibodies. Therefore, reducing pathogenic IgG levels by pharmacologic inhibition of FcRn may provide a novel approach for the treatment of immune complex-mediated glomerular diseases. As proof of concept, we showed that a peptide inhibiting the interaction between human FcRn and human IgG accelerated the degradation of human IgG anti-a3NC1 autoantibodies injected into FCRN-humanized mice as effectively as genetic ablation of FcRn, thus preventing the glomerular deposition of immune complexes containing human IgG.

show abstract

“…Each chain contains three structurally distinct domains; an aminoterminal domain rich in cysteine and lysine residues, a major collagenous region with Glycine-X-Y triple repeats of approximately 1,400 residues, followed by an about 230-residues long carboxy-terminal noncollagenous domain [3]. The NC1 domain can be considered as the initial director for the molecular assembly of the collagen-IV molecules [4,5]. However, the chains interact and assemble with a remarkable specificity to form only three distinct heterotrimers of 1 1 2, 3 4 5 and 5 5 6.…”

Section: Collagen-ivmentioning

confidence: 99%

Extracellular Matrix Proteins in the Anterior Pituitary Gland

Kanasaki¹

2011

TONEUROEJ

View full text Add to dashboard Cite

Abstract; The importance of the extracellular matrix (ECM) has become recognised as an important component of the functioning of cells. However the roles of the ECM in the anterior pituitary gland have received little attention. The pituitary has the particular characteristics of possessing a number of endocrine cells as well as less well studied nonendocrine cells. Because each cell has specific and vital roles in the physiology being of an individual the ECM must also possess selective activities. The details of ECM behaviour have not yet been delineated in the pituitary and this review first considers general characteristics of ECM compounds and then examines the properties of peptides with regard to functioning of the cells of the pituitary. It is noted that there are variations between ECM associated with normal cells and with tumours, that there are both morphological and biochemical responses to alterations in the composition of substrate on which cells are grown, and that a development of further models of ECM will be required for continued advances in the understanding of the manner in which the pituitary behaves in normal, clinical and pathological circumstances. Overall, the observations suggest that modulation of the ECM provides opportunities for enhancing well-being of individuals.

show abstract

Human Podocytes Adhere to the KRGDS Motif of the α3α4α5 Collagen IV Network

Cited by 32 publications

References 35 publications

Inhibition of Integrin α2β1 Ameliorates Glomerular Injury

Inhibition of Integrin α2β1 Ameliorates Glomerular Injury

Neonatal Fc Receptor Promotes Immune Complex–Mediated Glomerular Disease

Extracellular Matrix Proteins in the Anterior Pituitary Gland

Contact Info

Product

Resources

About