A network map of endothelin mediated signaling pathway

Dagamajalu, Shobha; Rex, Devasahayam Arokia Balaya; Gopalakrishnan, Lathika; Karthikkeyan, Gayathree; Gurtoo, Sumrati; Modi, Prashant Kumar; Mohanty,; Mujeeburahiman, M; Soman, Sowmya; Raju, Rajesh; Tiwari, Vinod; Prasad, T. S. Keshava

doi:10.1007/s12079-020-00581-4

Cited by 20 publications

(14 citation statements)

References 30 publications

(33 reference statements)

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“…The copyright holder for this this version posted September 16, 2021. ; https://doi.org/10.1101/2021.09.13.21263340 doi: medRxiv preprint interaction showed enrichment of genes in the signaling pathways of Rho GTPase small molecules, axon guidance, actin skeleton, VEGFA-NRP1 induced angiogenesis, and the endothelin-1 pathway. Identification of the endothlin-1 41 and TGFB1 pathways in our study is supported by prior literature on the role of these pathways in DKD susceptibility [42][43][44][45][46][47][48][49][50][51][52][53] . The Gas6-AKT pathway was shown to be involved in mesangial hypertrophy in rat models of DKD 54,55 .…”

Section: Discussionsupporting

confidence: 88%

Molecular Programs of Glomerular Hyperfiltration in Early Diabetic Kidney Disease

Stefansson

Nair

Melsom

et al. 2021

Preprint

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Hyperfiltration (HF) is a state of high glomerular filtration rate (GFR) observed in early diabetes that damages glomeruli, resulting in an iterative process of increasing filtration load on fewer and fewer remaining functional glomeruli. To delineate underlying cellular mechanisms of damage induced by HF, transcriptional profiles of kidney biopsies from Pima Indians with type 2 diabetes with or without early-stage diabetic kidney disease (DKD) were grouped into two HF categories based on annual iothalamate GFR measurements. Twenty-six participants with a peak GFR measurement within two years of biopsy were categorized as the HF group, and 26 in whom biopsy preceded peak GFR by >2 years were considered pre-HF. The HF group had higher hemoglobin A1c, higher urine albumin-to-creatinine ratio, increased glomerular basement membrane width and lower podocyte density compared to the pre-HF group. A glomerular 1240-gene transcriptional signature identified in the HF group was enriched for endothelial stress response signaling genes, including from endothelin-1, tec-kinase and TGF-β1 pathways, with the majority of the transcripts mapped to endothelial and inflammatory cell clusters in kidney single cell transcriptional data. This analysis reveals molecular pathomechanisms contributing to development of HF and early DKD and involving putative ligand-receptor pairs and downstream intracellular targets linked to cellular crosstalk between endothelial and mesangial cells.

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Section: Discussionsupporting

confidence: 88%

Molecular Programs of Glomerular Hyperfiltration in Early Diabetic Kidney Disease

Stefansson

Nair

Melsom

et al. 2021

Preprint

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show abstract

“…Mesangial cells targeted by this receptor-ligand interaction showed enrichment of genes in the signaling pathways of Rho GTPase small J o u r n a l P r e -p r o o f molecules, axon guidance, actin skeleton, VEGFA-NRP1 induced angiogenesis, and the endothelin-1 pathway. Identification of the endothlin-1 42 and TGFB1 pathways in our study is supported by prior literature on the role of these pathways in DKD susceptibility [43][44][45][46][47][48][49][50][51][52][53][54] . The Gas6-AKT pathway was shown to be involved in mesangial hypertrophy in rat models of DKD 55,56 .…”

Section: Discussionsupporting

confidence: 87%

Molecular programs associated with glomerular hyperfiltration in early diabetic kidney disease

Stefansson

Nair

Melsom

et al. 2022

Kidney International

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“…Apelin encodes a 77-residue prepropeptide. The apelin propeptide contains several proteolytic cleavage sites, which can generate carboxy-terminal peptides, including apelin-36, apelin-17, apelin-13, and apelin-12 [ 19 , 20 ]. Among them, apelin-13 has the strongest biological activity, and apelin-36 was first identified from a bovine stomach extract in 1998.…”

Section: Discussionmentioning

confidence: 99%

Amidation-Modified Apelin-13 Regulates PPARγ and Perilipin to Inhibit Adipogenic Differentiation and Promote Lipolysis

Wang

Gao

et al. 2021

Bioinorganic Chemistry and Applications

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With the adjustment of human diet and lifestyle changes, the prevalence of obesity is increasing year by year. Obesity is closely related to the excessive accumulation of white adipose tissue (WAT), which can synthesize and secrete a variety of adipokines. Apelin is a biologically active peptide in the adipokines family. Past studies have shown that apelin plays an important regulatory role in the pathogenesis and pathophysiology of diseases such as the cardiovascular system, respiratory system, digestive system, nervous system, and endocrine system. Apelin is also closely related to diabetes and obesity. Therefore, we anticipate that apelin-13 has an effect on lipometabolism and intend to explore the effect of apelin-13 on lipometabolism at the cellular and animal levels. In in vitro experiments, amidation-modified apelin-13 can significantly reduce the lipid content; TG content; and the expression of PPARγ, perilipin mRNA, and protein in adipocytes. Animal experiments also show that amidation modification apelin-13 can improve the abnormal biochemical indicators of diet-induced obesity (DOI) rats and can reduce the average diameter of adipocytes in adipose tissue, the concentration of glycerol, and the expression of PPARγ and perilipin mRNA and protein. Our results show that apelin-13 can affect the metabolism of adipose tissue, inhibit adipogenic differentiation of adipocytes, promote lipolysis, and thereby improve obesity. The mechanism may be regulating the expression of PPARγ to inhibit adipogenic differentiation and regulating the expression of perilipin to promote lipolysis. This study helps us understand the role of apelin-13 in adipose tissue and provide a basis for the elucidation of the regulation mechanism of lipometabolism and the development of antiobesity drugs.

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A network map of endothelin mediated signaling pathway

Cited by 20 publications

References 30 publications

Molecular Programs of Glomerular Hyperfiltration in Early Diabetic Kidney Disease

Molecular Programs of Glomerular Hyperfiltration in Early Diabetic Kidney Disease

Molecular programs associated with glomerular hyperfiltration in early diabetic kidney disease

Amidation-Modified Apelin-13 Regulates PPARγ and Perilipin to Inhibit Adipogenic Differentiation and Promote Lipolysis

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