PKD1 regulates a number of cellular processes through the formation of complexes with the PKD2 ion channel or transient receptor potential classical (TRPC) 4 in the endothelial cells. Although Ca 2+ modulation by polycystins has been reported between PKD1 and TRPC4 channel or TRPC1 and PKD2, the function with TRPC subfamily regulated by PKD2 has remained elusive. We confirmed TRPC4 or TRPC5 channel activation via PKD1 by modulating G-protein signaling without change in TRPC4/C5 translocation. The activation of TRPC4/C5 channels by intracellular 0.2 mM GTPγS was not significantly different regardless of the presence or absence of PKD1. Furthermore, the C-terminal fragment (CTF) of PKD1 did not affect TRPC4/C5 activity, likely due to the loss of the N-terminus that contains the G-protein coupled receptor proteolytic site (GPS). We also investigated whether TRPC1/C4/C5 can form a heterodimeric channel with PKD2, despite PKD2 being primarily retained in the endoplasmic reticulum (ER). Our findings show that PKD2 is targeted to the plasma membrane, particularly by TRPC5, but not by TRPC1. However, PKD2 did not coimmunoprecipitate with TRPC5 as well as with TRPC1. PKD2 decreased both basal and La 3+ -induced TRPC5 currents but increased M 3 R-mediated TRPC5 currents. Interestingly, PKD2 increased STAT3 phosphorylation with TRPC5 and decreased STAT1 phosphorylation with TRPC1. To be specific, PKD2 and TRPC1 compete to bind with TRPC5 to modulate intracellular Ca 2+ signaling and reach the plasma membrane. This interaction suggests a new therapeutic target in TRPC5 channels for improving vascular endothelial function in polycystic kidney disease.

PKD1 regulates a number of cellular processes through the formation of complexes with the PKD2 ion channel or transient receptor potential classical (TRPC) 4 in the endothelial cells. Although Ca 2+ modulation by polycystins has been reported between PKD1 and TRPC4 channel or TRPC1 and PKD2, the function with TRPC subfamily regulated by PKD2 has remained elusive. We confirmed TRPC4 or TRPC5 channel activation via PKD1 by modulating G-protein signaling without change in TRPC4/C5 translocation. The activation of TRPC4/C5 channels by intracellular 0.2 mM GTPγS was not significantly different regardless of the presence or absence of PKD1. Furthermore, the C-terminal fragment (CTF) of PKD1 did not affect TRPC4/C5 activity, likely due to the loss of the N-terminus that contains the G-protein coupled receptor proteolytic site (GPS). We also investigated whether TRPC1/C4/C5 can form a heterodimeric channel with PKD2, despite PKD2 being primarily retained in the endoplasmic reticulum (ER). Our findings show that PKD2 is targeted to the plasma membrane, particularly by TRPC5, but not by TRPC1. However, PKD2 did not coimmunoprecipitate with TRPC5 as well as with TRPC1. PKD2 decreased both basal and La 3+ -induced TRPC5 currents but increased M 3 R-mediated TRPC5 currents. Interestingly, PKD2 increased STAT3 phosphorylation with TRPC5 and decreased STAT1 phosphorylation with TRPC1. To be specific, PKD2 and TRPC1 compete to bind with TRPC5 to modulate intracellular Ca 2+ signaling and reach the plasma membrane. This interaction suggests a new therapeutic target in TRPC5 channels for improving vascular endothelial function in polycystic kidney disease.

PKD1 regulates a number of cellular processes through the formation of complexes with the PKD2 ion channel or transient receptor potential classical (TRPC) 4 in the endothelial cells. Although Ca 2+ modulation by polycystins has been reported between PKD1 and TRPC4 channel or TRPC1 and PKD2, the function with TRPC subfamily regulated by PKD2 has remained elusive. We confirmed TRPC4 or TRPC5 channel activation via PKD1 by modulating G-protein signaling without change in TRPC4/C5 translocation. The activation of TRPC4/C5 channels by intracellular 0.2 mM GTPγS was not significantly different regardless of the presence or absence of PKD1. Furthermore, the C-terminal fragment (CTF) of PKD1 did not affect TRPC4/C5 activity, likely due to the loss of the N-terminus that contains the G-protein coupled receptor proteolytic site (GPS). We also investigated whether TRPC1/C4/C5 can form a heterodimeric channel with PKD2, despite PKD2 being primarily retained in the endoplasmic reticulum (ER). Our findings show that PKD2 is targeted to the plasma membrane, particularly by TRPC5, but not by TRPC1. However, PKD2 did not coimmunoprecipitate with TRPC5 as well as with TRPC1. PKD2 decreased both basal and La 3+ -induced TRPC5 currents but increased M 3 R-mediated TRPC5 currents. Interestingly, PKD2 increased STAT3 phosphorylation with TRPC5 and decreased STAT1 phosphorylation with TRPC1. To be specific, PKD2 and TRPC1 compete to bind with TRPC5 to modulate intracellular Ca 2+ signaling and reach the plasma membrane. This interaction suggests a new therapeutic target in TRPC5 channels for improving vascular endothelial function in polycystic kidney disease.

PKD1 regulates a number of cellular processes through the formation of complexes with the PKD2 ion channel or transient receptor potential classical (TRPC) 4 in the endothelial cells. Although Ca 2+ modulation by polycystins has been reported between PKD1 and TRPC4 channel or TRPC1 and PKD2, the function with TRPC subfamily regulated by PKD2 has remained elusive. We confirmed TRPC4 or TRPC5 channel activation via PKD1 by modulating G-protein signaling without change in TRPC4/C5 translocation. The activation of TRPC4/C5 channels by intracellular 0.2 mM GTPγS was not significantly different regardless of the presence or absence of PKD1. Furthermore, the C-terminal fragment (CTF) of PKD1 did not affect TRPC4/C5 activity, likely due to the loss of the N-terminus that contains the G-protein coupled receptor proteolytic site (GPS). We also investigated whether TRPC1/C4/C5 can form a heterodimeric channel with PKD2, despite PKD2 being primarily retained in the endoplasmic reticulum (ER). Our findings show that PKD2 is targeted to the plasma membrane, particularly by TRPC5, but not by TRPC1. However, PKD2 did not coimmunoprecipitate with TRPC5 as well as with TRPC1. PKD2 decreased both basal and La 3+ -induced TRPC5 currents but increased M 3 R-mediated TRPC5 currents. Interestingly, PKD2 increased STAT3 phosphorylation with TRPC5 and decreased STAT1 phosphorylation with TRPC1. To be specific, PKD2 and TRPC1 compete to bind with TRPC5 to modulate intracellular Ca 2+ signaling and reach the plasma membrane. This interaction suggests a new therapeutic target in TRPC5 channels for improving vascular endothelial function in polycystic kidney disease.

PKD1 regulates a number of cellular processes through the formation of complexes with the PKD2 ion channel or transient receptor potential classical (TRPC) 4 in the endothelial cells. Although Ca 2+ modulation by polycystins has been reported between PKD1 and TRPC4 channel or TRPC1 and PKD2, the function with TRPC subfamily regulated by PKD2 has remained elusive. We confirmed TRPC4 or TRPC5 channel activation via PKD1 by modulating G-protein signaling without change in TRPC4/C5 translocation. The activation of TRPC4/C5 channels by intracellular 0.2 mM GTPγS was not significantly different regardless of the presence or absence of PKD1. Furthermore, the C-terminal fragment (CTF) of PKD1 did not affect TRPC4/C5 activity, likely due to the loss of the N-terminus that contains the G-protein coupled receptor proteolytic site (GPS). We also investigated whether TRPC1/C4/C5 can form a heterodimeric channel with PKD2, despite PKD2 being primarily retained in the endoplasmic reticulum (ER). Our findings show that PKD2 is targeted to the plasma membrane, particularly by TRPC5, but not by TRPC1. However, PKD2 did not coimmunoprecipitate with TRPC5 as well as with TRPC1. PKD2 decreased both basal and La 3+ -induced TRPC5 currents but increased M 3 R-mediated TRPC5 currents. Interestingly, PKD2 increased STAT3 phosphorylation with TRPC5 and decreased STAT1 phosphorylation with TRPC1. To be specific, PKD2 and TRPC1 compete to bind with TRPC5 to modulate intracellular Ca 2+ signaling and reach the plasma membrane. This interaction suggests a new therapeutic target in TRPC5 channels for improving vascular endothelial function in polycystic kidney disease.

Background: Thyroid function tests (TFT) produce varying results depending on the method, complicating standardization due to the lack of reference materials and methods. This study aims to harmonize TFT methods by deriving a recalibration equation using percentile transformation. Methods: Data from the Korean Association of External Quality Assessment Service (2017–2020) were analyzed, focusing on the three most used automated immunoassay analyzers. Outliers were excluded, and data were transformed into percentiles. A recalibration equation was derived through regression analysis, and the harmonization of results before and after recalibration was evaluated. Clinical sample measurements using the three methods and their reference intervals were applied to the recalibration equation. Results: Before recalibration, significant differences between methods were observed: 1.08 to 2.67 μIU/mL thyroid-stimulating hormone (TSH), 0.17 to 0.49 ng/mL triiodothyronine (T3), and 0.08 to 0.63 ng/dL free thyroxine (FT4).After recalibration, these differences were significantly reduced to 0.09 to 0.23 μIU/mL TSH, 0.002 to 0.006 ng/mL T3, and −0.01 to 0.02 ng/dL FT4.The distribution of clinical sample results remained consistent based on the reference interval before and after recalibration. However, differences persisted when applying clinical sample results to the recalibration equation. The difference in the TSH reference interval increased after recalibration, whereas the FT4 reference interval aligned more closely between methods. Conclusions Future studies should include multiple centers, sufficient clinical samples with various result levels, and multiple reagent lots. These studies should derive recalibration equations, and results from healthy individuals using various methods should be applied to establish a common reference interval.

Background: Thyroid function tests (TFT) produce varying results depending on the method, complicating standardization due to the lack of reference materials and methods. This study aims to harmonize TFT methods by deriving a recalibration equation using percentile transformation. Methods: Data from the Korean Association of External Quality Assessment Service (2017–2020) were analyzed, focusing on the three most used automated immunoassay analyzers. Outliers were excluded, and data were transformed into percentiles. A recalibration equation was derived through regression analysis, and the harmonization of results before and after recalibration was evaluated. Clinical sample measurements using the three methods and their reference intervals were applied to the recalibration equation. Results: Before recalibration, significant differences between methods were observed: 1.08 to 2.67 μIU/mL thyroid-stimulating hormone (TSH), 0.17 to 0.49 ng/mL triiodothyronine (T3), and 0.08 to 0.63 ng/dL free thyroxine (FT4).After recalibration, these differences were significantly reduced to 0.09 to 0.23 μIU/mL TSH, 0.002 to 0.006 ng/mL T3, and −0.01 to 0.02 ng/dL FT4.The distribution of clinical sample results remained consistent based on the reference interval before and after recalibration. However, differences persisted when applying clinical sample results to the recalibration equation. The difference in the TSH reference interval increased after recalibration, whereas the FT4 reference interval aligned more closely between methods. Conclusions Future studies should include multiple centers, sufficient clinical samples with various result levels, and multiple reagent lots. These studies should derive recalibration equations, and results from healthy individuals using various methods should be applied to establish a common reference interval.

Background: Thyroid function tests (TFT) produce varying results depending on the method, complicating standardization due to the lack of reference materials and methods. This study aims to harmonize TFT methods by deriving a recalibration equation using percentile transformation. Methods: Data from the Korean Association of External Quality Assessment Service (2017–2020) were analyzed, focusing on the three most used automated immunoassay analyzers. Outliers were excluded, and data were transformed into percentiles. A recalibration equation was derived through regression analysis, and the harmonization of results before and after recalibration was evaluated. Clinical sample measurements using the three methods and their reference intervals were applied to the recalibration equation. Results: Before recalibration, significant differences between methods were observed: 1.08 to 2.67 μIU/mL thyroid-stimulating hormone (TSH), 0.17 to 0.49 ng/mL triiodothyronine (T3), and 0.08 to 0.63 ng/dL free thyroxine (FT4).After recalibration, these differences were significantly reduced to 0.09 to 0.23 μIU/mL TSH, 0.002 to 0.006 ng/mL T3, and −0.01 to 0.02 ng/dL FT4.The distribution of clinical sample results remained consistent based on the reference interval before and after recalibration. However, differences persisted when applying clinical sample results to the recalibration equation. The difference in the TSH reference interval increased after recalibration, whereas the FT4 reference interval aligned more closely between methods. Conclusions Future studies should include multiple centers, sufficient clinical samples with various result levels, and multiple reagent lots. These studies should derive recalibration equations, and results from healthy individuals using various methods should be applied to establish a common reference interval.

Background: Thyroid function tests (TFT) produce varying results depending on the method, complicating standardization due to the lack of reference materials and methods. This study aims to harmonize TFT methods by deriving a recalibration equation using percentile transformation. Methods: Data from the Korean Association of External Quality Assessment Service (2017–2020) were analyzed, focusing on the three most used automated immunoassay analyzers. Outliers were excluded, and data were transformed into percentiles. A recalibration equation was derived through regression analysis, and the harmonization of results before and after recalibration was evaluated. Clinical sample measurements using the three methods and their reference intervals were applied to the recalibration equation. Results: Before recalibration, significant differences between methods were observed: 1.08 to 2.67 μIU/mL thyroid-stimulating hormone (TSH), 0.17 to 0.49 ng/mL triiodothyronine (T3), and 0.08 to 0.63 ng/dL free thyroxine (FT4).After recalibration, these differences were significantly reduced to 0.09 to 0.23 μIU/mL TSH, 0.002 to 0.006 ng/mL T3, and −0.01 to 0.02 ng/dL FT4.The distribution of clinical sample results remained consistent based on the reference interval before and after recalibration. However, differences persisted when applying clinical sample results to the recalibration equation. The difference in the TSH reference interval increased after recalibration, whereas the FT4 reference interval aligned more closely between methods. Conclusions Future studies should include multiple centers, sufficient clinical samples with various result levels, and multiple reagent lots. These studies should derive recalibration equations, and results from healthy individuals using various methods should be applied to establish a common reference interval.

Background: Thyroid function tests (TFT) produce varying results depending on the method, complicating standardization due to the lack of reference materials and methods. This study aims to harmonize TFT methods by deriving a recalibration equation using percentile transformation. Methods: Data from the Korean Association of External Quality Assessment Service (2017–2020) were analyzed, focusing on the three most used automated immunoassay analyzers. Outliers were excluded, and data were transformed into percentiles. A recalibration equation was derived through regression analysis, and the harmonization of results before and after recalibration was evaluated. Clinical sample measurements using the three methods and their reference intervals were applied to the recalibration equation. Results: Before recalibration, significant differences between methods were observed: 1.08 to 2.67 μIU/mL thyroid-stimulating hormone (TSH), 0.17 to 0.49 ng/mL triiodothyronine (T3), and 0.08 to 0.63 ng/dL free thyroxine (FT4).After recalibration, these differences were significantly reduced to 0.09 to 0.23 μIU/mL TSH, 0.002 to 0.006 ng/mL T3, and −0.01 to 0.02 ng/dL FT4.The distribution of clinical sample results remained consistent based on the reference interval before and after recalibration. However, differences persisted when applying clinical sample results to the recalibration equation. The difference in the TSH reference interval increased after recalibration, whereas the FT4 reference interval aligned more closely between methods. Conclusions Future studies should include multiple centers, sufficient clinical samples with various result levels, and multiple reagent lots. These studies should derive recalibration equations, and results from healthy individuals using various methods should be applied to establish a common reference interval.