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Uremic serum-induced calcification of human aortic smooth muscle cells is a regulated process involving Klotho and RUNX2. / Patidar, Ashish; Singh, Dhruv K; Thakur, Shori; Farrington, Ken; Baydoun, Anwar R.

In: Bioscience Reports, Vol. 39, No. 10, BSR20190599, 11.10.2019, p. 1-11.

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@article{c39f54af3a4046b0bbd1967b7c3f03a9,
title = "Uremic serum-induced calcification of human aortic smooth muscle cells is a regulated process involving Klotho and RUNX2",
abstract = "Vascular calcification (VC) is common in subjects with chronic kidney disease (CKD) and is associated with increased cardiovascular risk. It is an active process involving transdifferentiation of arterial smooth muscle cells (SMCs) into osteogenic phenotype. We investigated the ability of serum from CKD subjects to induce calcification in human SMCs in vitro (calcific potential of sera: CP), and associated changes in expression of Runt-related transcription factor 2 (RUNX2), SM22a, and Klotho. Sera from subjects with CKD (18 stage 3, 17 stage 4/5, and 29 stage 5D) and 20 controls were added to human cultured SMCs and CP quantified. The CP of CKD sera was greater (P>0.01) than that of controls, though not influenced by CKD stage. Modification of diet in renal disease estimated glomerular filtration rate (MDRD-4 eGFR) (P>0.001), serum phosphate (P=0.042), receptor activator of nuclear factor ?appa-B ligand (RANKL) (P=0.001), parathyroid hormone (PTH) (P=0.014), and high-density lipoprotein (HDL)/cholesterol ratio (P=0.026) were independent predictors of CP accounting for 45% of variation. Adding calcification buffer (CB: calcium chloride [7 mM] and β-glycerophosphate [7 mM]) increased the CP of control sera to approximate that of CKD sera. CP of CKD sera was unchanged. CKD sera increased RUNX2 expression (P>0.01) in human SMCs and decreased SM22a expression (P>0.05). Co-incubating control but not CKD serum with CB further increased RUNX2 expression (P>0.01). Both SM22a and Klotho expression decreased significantly (P>0.01) in the presence of CKD serum, and were virtually abolished with stage 5D sera. These findings support active regulation by CKD serum of in vitro VC by induction of RUNX2 and suppression of SM22a and Klotho.",
author = "Ashish Patidar and Singh, {Dhruv K} and Shori Thakur and Ken Farrington and Baydoun, {Anwar R}",
note = "{\textcopyright} 2019 The Author(s). This is an open access article published by Portland Press Limited on behalf of the Biochemical Society and distributed under the Creative Commons Attribution License 4.0 (CC BY). ",
year = "2019",
month = oct,
day = "11",
doi = "10.1042/BSR20190599",
language = "English",
volume = "39",
pages = "1--11",
journal = "Bioscience Reports",
issn = "0144-8463",
publisher = "Portland Press Ltd.",
number = "10",

}

RIS

TY - JOUR

T1 - Uremic serum-induced calcification of human aortic smooth muscle cells is a regulated process involving Klotho and RUNX2

AU - Patidar, Ashish

AU - Singh, Dhruv K

AU - Thakur, Shori

AU - Farrington, Ken

AU - Baydoun, Anwar R

N1 - © 2019 The Author(s). This is an open access article published by Portland Press Limited on behalf of the Biochemical Society and distributed under the Creative Commons Attribution License 4.0 (CC BY).

PY - 2019/10/11

Y1 - 2019/10/11

N2 - Vascular calcification (VC) is common in subjects with chronic kidney disease (CKD) and is associated with increased cardiovascular risk. It is an active process involving transdifferentiation of arterial smooth muscle cells (SMCs) into osteogenic phenotype. We investigated the ability of serum from CKD subjects to induce calcification in human SMCs in vitro (calcific potential of sera: CP), and associated changes in expression of Runt-related transcription factor 2 (RUNX2), SM22a, and Klotho. Sera from subjects with CKD (18 stage 3, 17 stage 4/5, and 29 stage 5D) and 20 controls were added to human cultured SMCs and CP quantified. The CP of CKD sera was greater (P>0.01) than that of controls, though not influenced by CKD stage. Modification of diet in renal disease estimated glomerular filtration rate (MDRD-4 eGFR) (P>0.001), serum phosphate (P=0.042), receptor activator of nuclear factor ?appa-B ligand (RANKL) (P=0.001), parathyroid hormone (PTH) (P=0.014), and high-density lipoprotein (HDL)/cholesterol ratio (P=0.026) were independent predictors of CP accounting for 45% of variation. Adding calcification buffer (CB: calcium chloride [7 mM] and β-glycerophosphate [7 mM]) increased the CP of control sera to approximate that of CKD sera. CP of CKD sera was unchanged. CKD sera increased RUNX2 expression (P>0.01) in human SMCs and decreased SM22a expression (P>0.05). Co-incubating control but not CKD serum with CB further increased RUNX2 expression (P>0.01). Both SM22a and Klotho expression decreased significantly (P>0.01) in the presence of CKD serum, and were virtually abolished with stage 5D sera. These findings support active regulation by CKD serum of in vitro VC by induction of RUNX2 and suppression of SM22a and Klotho.

AB - Vascular calcification (VC) is common in subjects with chronic kidney disease (CKD) and is associated with increased cardiovascular risk. It is an active process involving transdifferentiation of arterial smooth muscle cells (SMCs) into osteogenic phenotype. We investigated the ability of serum from CKD subjects to induce calcification in human SMCs in vitro (calcific potential of sera: CP), and associated changes in expression of Runt-related transcription factor 2 (RUNX2), SM22a, and Klotho. Sera from subjects with CKD (18 stage 3, 17 stage 4/5, and 29 stage 5D) and 20 controls were added to human cultured SMCs and CP quantified. The CP of CKD sera was greater (P>0.01) than that of controls, though not influenced by CKD stage. Modification of diet in renal disease estimated glomerular filtration rate (MDRD-4 eGFR) (P>0.001), serum phosphate (P=0.042), receptor activator of nuclear factor ?appa-B ligand (RANKL) (P=0.001), parathyroid hormone (PTH) (P=0.014), and high-density lipoprotein (HDL)/cholesterol ratio (P=0.026) were independent predictors of CP accounting for 45% of variation. Adding calcification buffer (CB: calcium chloride [7 mM] and β-glycerophosphate [7 mM]) increased the CP of control sera to approximate that of CKD sera. CP of CKD sera was unchanged. CKD sera increased RUNX2 expression (P>0.01) in human SMCs and decreased SM22a expression (P>0.05). Co-incubating control but not CKD serum with CB further increased RUNX2 expression (P>0.01). Both SM22a and Klotho expression decreased significantly (P>0.01) in the presence of CKD serum, and were virtually abolished with stage 5D sera. These findings support active regulation by CKD serum of in vitro VC by induction of RUNX2 and suppression of SM22a and Klotho.

UR - http://www.scopus.com/inward/record.url?scp=85074184478&partnerID=8YFLogxK

U2 - 10.1042/BSR20190599

DO - 10.1042/BSR20190599

M3 - Article

C2 - 31519772

VL - 39

SP - 1

EP - 11

JO - Bioscience Reports

JF - Bioscience Reports

SN - 0144-8463

IS - 10

M1 - BSR20190599

ER -