RGD Reference Report - Protein S Protects against Podocyte Injury in Diabetic Nephropathy. - Rat Genome Database

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Protein S Protects against Podocyte Injury in Diabetic Nephropathy.

Authors: Zhong, Fang  Chen, Haibing  Xie, Yifan  Azeloglu, Evren U  Wei, Chengguo  Zhang, Weijia  Li, Zhengzhe  Chuang, Peter Y  Jim, Belinda  Li, Hong  Elmastour, Firas  Riyad, Jalish M  Weber, Thomas  Chen, Hongyu  Wang, Yongjun  Zhang, Aihua  Jia, Weiping  Lee, Kyung  He, John C 
Citation: Zhong F, etal., J Am Soc Nephrol. 2018 Mar 6. pii: ASN.2017030234. doi: 10.1681/ASN.2017030234.
RGD ID: 13515131
Pubmed: PMID:29511111   (View Abstract at PubMed)
PMCID: PMC5967770   (View Article at PubMed Central)
DOI: DOI:10.1681/ASN.2017030234   (Journal Full-text)

Background Diabetic nephropathy (DN) is a leading cause of ESRD in the United States, but the molecular mechanisms mediating the early stages of DN are unclear.MethodsTo assess global changes that occur in early diabetic kidneys and to identify proteins potentially involved in pathogenic pathways in DN progression, we performed proteomic analysis of diabetic and nondiabetic rat glomeruli. Protein S (PS) among the highly upregulated proteins in the diabetic glomeruli. PS exerts multiple biologic effects through the Tyro3, Axl, and Mer (TAM) receptors. Because increased activation of Axl by the PS homolog Gas6 has been implicated in DN progression, we further examined the role of PS in DN.ResultsIn human kidneys, glomerular PS expression was elevated in early DN but suppressed in advanced DN. However, plasma PS concentrations did not differ between patients with DN and healthy controls. A prominent increase of PS expression also colocalized with the expression of podocyte markers in early diabetic kidneys. In cultured podocytes, high-glucose treatment elevated PS expression, and PS knockdown further enhanced the high-glucose-induced apoptosis. Conversely, PS overexpression in cultured podocytes dampened the high-glucose- and TNF-α-induced expression of proinflammatory mediators. Tyro3 receptor was upregulated in response to high glucose and mediated the anti-inflammatory response of PS. Podocyte-specific PS loss resulted in accelerated DN in streptozotocin-induced diabetic mice, whereas the transient induction of PS expression in glomerular cellsin vivoattenuated albuminuria and podocyte loss in diabetic OVE26 mice.ConclusionsOur results support a protective role of PS against glomerular injury in DN progression.

Disease Annotations    
Diabetic Nephropathies  (IEP,IMP,ISO)

Objects Annotated

Genes (Rattus norvegicus)
Pros1  (protein S)

Genes (Mus musculus)
Pros1  (protein S (alpha))

Genes (Homo sapiens)
PROS1  (protein S)

Additional Information