Steap4 attenuates high glucose and S100B‐induced effects in mesangial cells

Chuang, Chao-Tang; Guh, Jinn‐Yuh; Lu, Chi‐Yu; Wang, Yeng‐Tseng; Chen, Hung‐Chun; Chuang, Li‐Yeh

doi:10.1111/jcmm.12472

Cited by 13 publications

(13 citation statements)

References 41 publications

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“…Similarly, Steap4 has also been reported to interact with BNIP3L (Passer et al 2003), focal adhesion kinase-1(Tamura & Chiba 2009) and S100B (Chuang et al. 2015), again suggesting possible links to apoptosis, differentiation and cell cycle progression.…”

Section: Steap4 In Metabolic Disordersmentioning

confidence: 92%

“…Emerging evidence has demonstrated a role for STEAP4 in the cellular response to nutritional and inflammatory signals (Wellen et al 2007). When overexpressed, STEAP4 has been shown to reduce inflammation and better regulate glucose metabolism in a mouse model of streptozotocin-induced diabetes (Chuang et al 2015). In another study, STEAP4 overexpression shifted macrophage polarization to enhance protection of adipose tissue, leading to reduced insulin resistance in diabetic ApoE − / − /LDLR − / − mice (Han et al 2013).…”

Section: Steap4 Tissue and Cellular Expressionmentioning

confidence: 99%

“…These transcription factors are activated in response to inflammatory and nutritional signals, suggesting that STEAP4 might play a protective role at the cellular or systemic level (Ramadoss et al 2010). Similarly, in mesangial cells where high glucose induces Steap4 expression, the increased expression was found to be dependent upon S100B, JNK, PI3K, JAK2 and STAT3 (Chuang et al 2015). …”

Section: Regulatory Influences On Steap4 Expressionmentioning

confidence: 99%

“…For example, in the mesangial cells discussed immediately above, STEAP4 overexpression attenuates high glucose induced expression of collagen IV, fibronectin and COX2, as well as the expression of TGF-β, ERK1/2, Akt, Smad2/3 and STAT3 (Chuang et al 2015). The observation that high glucose induces STAT3 dependent expression of STEAP4 (above), and that overexpression of STEAP4 in turn attenuates expression of STAT3, as well as other important signaling molecules like TGF-β, ERK1/2, Akt and Smad2/3, suggests STEAP4 may participate in a feedback loop that modulates the effects of high glucose on mesangial cells.…”

Section: Regulatory and Protective Influences Of Steap4mentioning

confidence: 99%

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STEAP4: its emerging role in metabolism and homeostasis of cellular iron and copper

Scarl

Lawrence

Gordon

et al. 2017

Journal of Endocrinology

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Preserving energy homeostasis in the presence of stressors such as proinflammatory cytokines and nutrient overload is crucial to maintaining normal cellular function. Six-transmembrane epithelial antigen of the prostate 4 (STEAP4), a metalloreductase involved in iron and copper homeostasis, is thought to play a potentially important role in the cellular response to inflammatory stress. Genome-wide association studies have linked various mutations in STEAP4 with the development of metabolic disorders such as obesity, metabolic syndrome, and type 2 diabetes. Several studies have shown that expression of Steap4 is modulated by inflammatory cytokines, hormones, and other indicators of cellular stress, and that STEAP4 may protect cells from damage, helping to maintain normal metabolic function. STEAP4 appears to be particularly relevant in metabolically oriented cells, such as adipocytes, hepatocytes, and pancreatic islet cells. These cells struggle to maintain their function in iron or copper overloaded states, presumably due to increased oxidative stress, suggesting STEAP4’s role in metal homeostasisis critical to the maintenance of cellular homeostasis in general, and in preventing the onset of metabolic disease. In this review, we explore genetic associations of STEAP4 with metabolic disorders, and we examine STEAP4 tissue expression, subcellular localization, regulation, structure, and function as it relates to metabolic diseases. We then examine how STEAP4’s role as a regulator of cellular iron and copper may relate to type 2 diabetes.

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Section: Steap4 In Metabolic Disordersmentioning

confidence: 92%

Section: Steap4 Tissue and Cellular Expressionmentioning

confidence: 99%

Section: Regulatory Influences On Steap4 Expressionmentioning

confidence: 99%

Section: Regulatory and Protective Influences Of Steap4mentioning

confidence: 99%

See 2 more Smart Citations

STEAP4: its emerging role in metabolism and homeostasis of cellular iron and copper

Scarl

Lawrence

Gordon

et al. 2017

Journal of Endocrinology

View full text Add to dashboard Cite

show abstract

“…A number of genome-wide association studies suggest that STEAP4 is involved with numerous disorders related to obesity and metabolism including insulin resistance [8,9], metabolic syndrome [10,11], and insulin secretion [12,13]. Beyond its known role as a metalloreductase [14], studies have shown that STEAP4 plays an anti-inflammatory or protective role from cellular damage in adipocytes [15,9], mesangial cells [16], hepatocytes [17–19], and synoviocytes [20]. In studies of mice, the STEAP4-/- phenotype includes the spontaneous development of obesity, insulin resistance, and eventual hyperglycemia [21], as well as signs of atherosclerosis [22], also suggesting a protective role for the protein.…”

Section: Introductionmentioning

confidence: 99%

STEAP4 expression in human islets is associated with differences in body mass index, sex, HbA1c, and inflammation

et al. 2017

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Six-transmembrane epithelial antigen of the prostate 4 (STEAP4) is a metalloreductase that has been shown previously to protect cells from inflammatory damage. Genetic variants in STEAP4 have been associated with numerous metabolic disorders related to obesity, including putative defects in the acute insulin response to glucose in type 2 diabetes (T2D). Purpose We examined whether obesity and/or T2D altered STEAP4 expression in human pancreatic islets. Methods Human islets were isolated from deceased donors at two medical centers and processed for quantitative PCR. Organ donors were selected by status as non-diabetic or having T2D. Site1 (Edmonton): N=13 T2D donors (7M, 6F), N=20 non-diabetic donors (7M, 13F). Site2 (Virginia): N=6 T2D donors (6F), N=6 non-diabetic donors (3M, 3F). Results STEAP4 showed reduced islet expression with increasing BMI among all donors (P<0.10) and non-diabetic donors (P<0.05) from Site1; STEAP4 showed reduced islet expression among T2D donors with increasing HbA1c. Islet STEAP4 expression was also marginally higher in female donors (p<0.10). Among T2D donors from Site2, islet insulin expression was reduced, STEAP4 expression was increased, and white blood cell counts were increased compared to non-diabetic donors. Islets from non-diabetic donors that were exposed overnight to 5ng/ml IL-1β displayed increased STEAP4 expression, consistent with STEAP4 upregulation by inflammatory signaling. Conclusions These findings suggest that increased STEAP4 mRNA expression is associated with inflammatory stimuli, whereas lower STEAP4 expression is associated with obesity in human islets. Given its known protective role, downregulation of STEAP4 by chronic obesity suggests a mechanism for reduced islet protection against cellular damage.

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Glomerular basement membrane deposition of collagen α1(III) in Alport glomeruli by mesangial filopodia injures podocytes via aberrant signaling through DDR1 and integrin α2β1

Madison

Wilhelm

Meehan

et al. 2022

The Journal of Pathology

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In Alport mice, activation of the endothelin A receptor (ETAR) in mesangial cells results in sub‐endothelial invasion of glomerular capillaries by mesangial filopodia. Filopodia deposit mesangial matrix in the glomerular basement membrane (GBM), including laminin 211 which activates NF‐κB, resulting in induction of inflammatory cytokines. Herein we show that collagen α1(III) is also deposited in the GBM. Collagen α1(III) localized to the mesangium in wild‐type mice and was found in both the mesangium and the GBM in Alport mice. We show that collagen α1(III) activates discoidin domain receptor family, member 1 (DDR1) receptors both in vitro and in vivo. To elucidate whether collagen α1(III) might cause podocyte injury, cultured murine Alport podocytes were overlaid with recombinant collagen α1(III), or not, for 24 h and RNA was analyzed by RNA sequencing (RNA‐seq). These same cells were subjected to siRNA knockdown for integrin α2 or DDR1 and the RNA was analyzed by RNA‐seq. Results were validated in vivo using RNA‐seq from RNA isolated from wild‐type and Alport mouse glomeruli. Numerous genes associated with podocyte injury were up‐ or down‐regulated in both Alport glomeruli and cultured podocytes treated with collagen α1(III), 18 of which have been associated previously with podocyte injury or glomerulonephritis. The data indicate α2β1 integrin/DDR1 co‐receptor signaling as the dominant regulatory mechanism. This may explain earlier studies where deletion of either DDR1 or α2β1 integrin in Alport mice ameliorates renal pathology. © 2022 Boys Town National Research Hospital. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.

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Steap4 attenuates high glucose and S100B‐induced effects in mesangial cells

Cited by 13 publications

References 41 publications

STEAP4: its emerging role in metabolism and homeostasis of cellular iron and copper

STEAP4: its emerging role in metabolism and homeostasis of cellular iron and copper

STEAP4 expression in human islets is associated with differences in body mass index, sex, HbA1c, and inflammation

Glomerular basement membrane deposition of collagen α1(III) in Alport glomeruli by mesangial filopodia injures podocytes via aberrant signaling through DDR1 and integrin α2β1

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