| 1. |
- Ngo, Debby, et al.
(author)
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Circulating testican-2 is a podocyte-derived marker of kidney health
- 2020
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In: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 1091-6490 .- 0027-8424. ; 117:40, s. 25026-25035
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Journal article (peer-reviewed)abstract
- In addition to their fundamental role in clearance, the kidneys release select molecules into the circulation, but whether any of these anabolic functions provides insight on kidney health is unknown. Using aptamer-based proteomics, we characterized arterial (A)-to-renal venous (V) gradients for >1,300 proteins in 22 individuals who underwent invasive sampling. Although most of the proteins that changed significantly decreased from A to V, consistent with renal clearance, several were found to increase, the most significant of which was testican-2. To assess the clinical implications of these physiologic findings, we examined proteomic data in the Jackson Heart Study (JHS), an African-American cohort (n = 1,928), with replication in the Framingham Heart Study (FHS), a White cohort (n = 1,621). In both populations, testican-2 had a strong, positive correlation with estimated glomerular filtration rate (eGFR). In addition, higher baseline testican-2 levels were associated with a lower rate of eGFR decline in models adjusted for age, gender, hypertension, type 2 diabetes, body mass index, baseline eGFR, and albuminuria. Glomerular expression of testican-2 in human kidneys was demonstrated by immunohistochemistry, immunofluorescence, and electron microscopy, while single-cell RNA sequencing of human kidneys showed expression of the cognate gene, SPOCK2, exclusively in podocytes. In vitro, testican-2 increased glomerular endothelial tube formation and motility, raising the possibility that its secretion has a functional role within the glomerulus. Taken together, our findings identify testican-2 as a podocyte-derived biomarker of kidney health and prognosis.
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| 2. |
- Ngo, Debby, et al.
(author)
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Proteomic profiling reveals novel biomarkers and pathways in yype 2 diabetes risk
- 2021
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In: JCI Insight. - : American Society for Clinical Investigation. - 2379-3708. ; 6:5
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Journal article (peer-reviewed)abstract
- Recent advances in proteomic technologies have made high throughput profiling of low abundance proteins in large epidemiological cohorts increasingly feasible. We investigated whether aptamer-based proteomic profiling could identify biomarkers associated with future development of type 2 diabetes (T2DM) beyond known risk factors. We identified dozens of markers with highly significant associations with future T2DM across two large longitudinal cohorts (n=2,839) followed for up to 16 years. We leveraged proteomic, metabolomic, genetic and clinical data from humans to nominate one specific candidate to test for potential causal relationships in model systems. Our studies identified functional effects of aminoacylase 1 (ACY1), a top protein association with future T2DM risk, on amino acid metabolism and insulin homeostasis in vitro and in vivo. Further, a loss-of-function variant associated with circulating levels of the biomarker WAP, Kazal, immunoglobulin, Kunitz and NTR domain-containing protein 2 (WFIKKN2) was in turn associated with fasting glucose, hemoglobin A1c and HOMA-IR measurements in humans. In addition to identifying novel disease markers and potential pathways in T2DM, we provide publicly available data to be leveraged for new insights about gene function and disease pathogenesis in the context of human metabolism. .
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| 3. |
- Robbins, Jeremy M, et al.
(author)
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Plasma proteomic changes in response to exercise training are associated with cardiorespiratory fitness adaptations.
- 2023
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In: JCI insight. - 2379-3708. ; 8:7
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Journal article (peer-reviewed)abstract
- Regular exercise leads to widespread salutary effects, and there is increasing recognition that exercise-stimulated circulating proteins can impart health benefits. Despite this, limited data exist regarding the plasma proteomic changes that occur in response to regular exercise. Here, we perform large-scale plasma proteomic profiling in 654 healthy human study participants before and after a supervised, 20-week endurance exercise training intervention. We identify hundreds of circulating proteins that are modulated, many of which are known to be secreted. We highlight proteins involved in angiogenesis, iron homeostasis, and the extracellular matrix, many of which are novel, including training-induced increases in fibroblast activation protein (FAP), a membrane-bound and circulating protein relevant in body-composition homeostasis. We relate protein changes to training-induced maximal oxygen uptake adaptations and validate our top findings in an external exercise cohort. Furthermore, we show that FAP is positively associated with survival in 3 separate, population-based cohorts.
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| 4. |
- Trinh, Lena, et al.
(author)
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Favorable fatty acid composition in adipose tissue in healthy Iraqi- compared to Swedish-born men - a pilot study using MRI assessment
- 2022
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In: Adipocyte. - : Informa UK Limited. - 2162-3945 .- 2162-397X. ; 11:1, s. 153-163
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Journal article (peer-reviewed)abstract
- Middle Eastern immigrants are at high-risk for insulin resistance. Fatty acid composition (FAC) plays an important role in the development of insulin resistance but has not been investigated in people of Middle Eastern ancestry. Here, the aim was to assess the FAC in visceral and subcutaneous adipose tissue (VAT and SAT) in healthy Iraqi- and Swedish-born men using a magnetic resonance imaging (MRI) method.This case-control study included 23 Iraqi- and 15 Swedish-born middle-aged men, without cardiometabolic disease. Using multi-echo MRI of the abdomen, the fractions of saturated, monounsaturated, and polyunsaturated fatty acids (fSFA, fMUFA, and fPUFA) were estimated in VAT and SAT. SAT was further analyzed in deep and superficial compartments (dSAT and sSAT).In all depots, fPUFA was significantly higher and fSFA significantly lower in Iraqi men, independently of age and BMI. In both Iraqi- and Swedish-born men, higher fPUFA and lower fMUFA were found in sSAT vs. dSAT. Among Iraqi men only, higher fPUFA and lower fMUFA were found in SAT vs. VAT.Iraqi-born men presented a more favorable abdominal FAC compared to Swedish-born men. This MRI method also revealed different FACs in different abdominal depots. Our results may reflect a beneficial FAC in Middle Eastern immigrants.
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| 5. |
- Niemi, MEK, et al.
(author)
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- 2021
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