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Solute Carrier Transporters in Synovial Membrane and Hoffa’s Pad of Patients with Rheumatoid Arthritis Cover

Solute Carrier Transporters in Synovial Membrane and Hoffa’s Pad of Patients with Rheumatoid Arthritis

Archivum Immunologiae et Therapiae Experimentalis
Volume 72 (2024): Issue 1 (January 2024)
By: Damian Malinowski,  Katarzyna Piotrowska,  Marek Droździk and  Andrzej Pawlik  
Open Access
|Jun 2024

Figures & Tables

Fig 1.

Expression of SLC16A3, SLC19A1, SLC2A9, SLC22A18, SLC33A1, SLC7A5, SLC7A6, SLC02B1, and SLC04A1 membrane transporters in the SM. X: abbreviations of the examined SLC transporters superfamily. Y: RQ 2−ΔCT mean values (±SD); *p < 0.05. CT, cycle threshold; RA, rheumatoid arthritis; RQ, relative quantification; SD, standard deviation; SLC, solute carrier; SM, synovial membrane.
Expression of SLC16A3, SLC19A1, SLC2A9, SLC22A18, SLC33A1, SLC7A5, SLC7A6, SLC02B1, and SLC04A1 membrane transporters in the SM. X: abbreviations of the examined SLC transporters superfamily. Y: RQ 2−ΔCT mean values (±SD); *p < 0.05. CT, cycle threshold; RA, rheumatoid arthritis; RQ, relative quantification; SD, standard deviation; SLC, solute carrier; SM, synovial membrane.

Fig 2.

Expression of SLC15A2, SLC22A1, SLC22A3, SLC22A4, SLC22A5, SLC47A1, SLC51A, and SLC01C1 membrane transporters in the SM. X: abbreviations of the examined SLC transporters superfamily. Y: RQ 2−ΔCT mean values (±SD); *p < 0.05. CT, cycle threshold; RA, rheumatoid arthritis; RQ, relative quantification; SD, standard deviation; SLC, solute carrier; SM, synovial membrane.
Expression of SLC15A2, SLC22A1, SLC22A3, SLC22A4, SLC22A5, SLC47A1, SLC51A, and SLC01C1 membrane transporters in the SM. X: abbreviations of the examined SLC transporters superfamily. Y: RQ 2−ΔCT mean values (±SD); *p < 0.05. CT, cycle threshold; RA, rheumatoid arthritis; RQ, relative quantification; SD, standard deviation; SLC, solute carrier; SM, synovial membrane.

Fig 3.

Expression of SLC16A3, SLC19A1, SLC2A9, SLC22A18, SLC33A1, SLC7A5, SLC7A6, SLC02B1, and SLC04A1 membrane transporters in the Hoffa’s pad. X: abbreviations of the examined SLC transporters superfamily. Y: RQ 2−ΔCT mean values (±SD); *p < 0.05. CT, cycle threshold; RA, rheumatoid arthritis; RQ, relative quantification; SD, standard deviation; SLC, solute carrier.
Expression of SLC16A3, SLC19A1, SLC2A9, SLC22A18, SLC33A1, SLC7A5, SLC7A6, SLC02B1, and SLC04A1 membrane transporters in the Hoffa’s pad. X: abbreviations of the examined SLC transporters superfamily. Y: RQ 2−ΔCT mean values (±SD); *p < 0.05. CT, cycle threshold; RA, rheumatoid arthritis; RQ, relative quantification; SD, standard deviation; SLC, solute carrier.

Fig 4.

Expression of SLC15A2, SLC22A1, SLC22A3, SLC22A4, SLC22A5, SLC47A1, SLC51A, and SLC01C1 membrane transporters in the Hoffa’s pad. X: abbreviations of the examined SLC transporters superfamily. Y: RQ 2−ΔCT mean values (±SD); *p < 0.05. CT, cycle threshold; RA, Rheumatoid arthritis; RQ, relative quantification; SD, standard deviation; SLC, solute carrier.
Expression of SLC15A2, SLC22A1, SLC22A3, SLC22A4, SLC22A5, SLC47A1, SLC51A, and SLC01C1 membrane transporters in the Hoffa’s pad. X: abbreviations of the examined SLC transporters superfamily. Y: RQ 2−ΔCT mean values (±SD); *p < 0.05. CT, cycle threshold; RA, Rheumatoid arthritis; RQ, relative quantification; SD, standard deviation; SLC, solute carrier.

Fig 5.

Transporter protein levels in SM and HFPs samples from RA and OA patients for PEPT2, SLC19A1, and MATE1 proteins. Pixel intensity acquired by ImageJ software. *Student’s t-test; #Mann–Whitney U-test. HFPs, Hoffa’s fat pads; OA, osteoarthritis; RA, rheumatoid arthritis; SLC, solute carrier; SM, synovial membrane.
Transporter protein levels in SM and HFPs samples from RA and OA patients for PEPT2, SLC19A1, and MATE1 proteins. Pixel intensity acquired by ImageJ software. *Student’s t-test; #Mann–Whitney U-test. HFPs, Hoffa’s fat pads; OA, osteoarthritis; RA, rheumatoid arthritis; SLC, solute carrier; SM, synovial membrane.

Fig 6.

Transporter protein expressions in SM samples from RA and OA patients. Transporters expression in RA patients panels (a, c, and e); transporters expressions in OA SM samples panels: (b, d, and f); green arrows—positive reaction of epithelial cells, red arrows—positive reaction of synoviocytes, red star—positive reaction in blood vessels; scale bar 50 μm; only representative images are presented. OA, osteoarthritis; RA, rheumatoid arthritis; SM, synovial membrane.
Transporter protein expressions in SM samples from RA and OA patients. Transporters expression in RA patients panels (a, c, and e); transporters expressions in OA SM samples panels: (b, d, and f); green arrows—positive reaction of epithelial cells, red arrows—positive reaction of synoviocytes, red star—positive reaction in blood vessels; scale bar 50 μm; only representative images are presented. OA, osteoarthritis; RA, rheumatoid arthritis; SM, synovial membrane.

Fig 7.

Transporter protein expressions in HFPs samples from RA and OA patients. Transporters expression in RA patients panels (a, c, and e); transporters expressions in OA HFP samples panels: (b, d, and f); scale bar 50 μm; only representative images are presented. HFPs, Hoffa’s fat pads; OA, osteoarthritis; RA, rheumatoid arthritis.
Transporter protein expressions in HFPs samples from RA and OA patients. Transporters expression in RA patients panels (a, c, and e); transporters expressions in OA HFP samples panels: (b, d, and f); scale bar 50 μm; only representative images are presented. HFPs, Hoffa’s fat pads; OA, osteoarthritis; RA, rheumatoid arthritis.

Fig 8.

SLC transporters: transport type of PEPT2 (cotransporter), RFC1 (exchanger) and MATE1 (exchanger) and their substrates. MPP, 1-methyl-4-phenylpyridinium; SLC, solute carrier; TEA, tetraethylammonium.
SLC transporters: transport type of PEPT2 (cotransporter), RFC1 (exchanger) and MATE1 (exchanger) and their substrates. MPP, 1-methyl-4-phenylpyridinium; SLC, solute carrier; TEA, tetraethylammonium.

IRS values for transportation proteins expression in SM samples in RA and OA patients

ProteinRAOA
MedianAverageMin.Max.MedianAverageMin.Max
PEPT288.1341265.2509
RFC187.9341265.63112
MATE166.432965.85012

SLC transporters expression in SM and HFP

SM (mean ± SD)HFP (mean ± SD)p-value*
SLC0C1∆∆CT0.437 ± 0.371.332 ± 0.900.088
SLC02B131.462 ± 63.6641.233 ± 43.920.070
SLC04A114.388 ± 13.3135.838 ± 21.450.036
SLC2A96.197 ± 1.2210.295 ± 8.950.895
SLC7A513.45 ± 20.9031.441 ± 28.920.239
SLC7A618.971 ± 15.31121.553 ± 125.980.0005
SLC15A20.963 ± 1.052.6 ± 2.470.039
SLC16A3154.528 ± 206.3942.223 ± 30.480.041
SLC19A17.35 ± 9.3022.44 ± 15.000.006
SLC22A11.289 ± 2.281.101 ± 0.890.307
SLC22A30.491 ± 0.692.386 ± 1.840.010
SLC22A42.081 ± 1.724.371 ± 2.930.064
SLC22A51.569 ± 1.496.656 ± 3.960.0008
SLC22A1822.775 ± 16.898.694 ± 2.870.005
SLC33A19.382 ± 5.0125.173 ± 9.620.0008
SLC47A12.632 ± 2.844.3612 ± 2.180.225
SLC51A0.146 ± 0.170.397 ± 0.120.275

Correlation between the expression of SLC transporters in SM and clinical parameters

CRPWBCAge (years)Disease durationDAS28
SLC15A2R−0.2670.517−0.3850.017−0.217
p-value0.4880.1540.3060.9650.576
SLC22A18R0.188−0.2000.261−0.1180.176
p-value0.6030.5800.4660.7460.627
SLC16A3R0.006−0.091−0.1760.285−0.018
p-value0.9870.8030.6260.4250.960
SLC33A1R0.261−0.3820.1220.4150.188
p-value0.4670.2760.7380.2330.603
SLC19A1R−0.3570.5480.1900.400−0.333
p-value0.3850.1600.6510.3260.420
SLC47A1R−0.3210.214−0.5000.436−0.250
p-value0.4820.6450.2530.3280.589
SLC2A9R−0.7830.100−0.393−0.339−0.767
p-value0.0130.7980.2950.3720.016
SLC51AR1.0000.500−0.500−0.8661.000
p-value−0.6670.6670.333−
SLC22A1R−0.2380.595−0.1320.146−0.238
p-value0.5700.1200.7560.7290.570
SLC22A3R−0.4640.4290.2140.436−0.429
p-value0.2940.3370.6450.3280.337
SLC7A5R−0.0500.333−0.5190.373−0.033
p-value0.8980.3810.1520.3230.932
SLC22A4R0.0360.036−0.2860.7640.036
p-value0.9390.9390.5350.0460.939
SLC7A6R0.2000.4550.1950.4150.212
p-value0.5800.1870.5900.2330.556
SLC22A5R−0.350−0.0330.2590.602−0.333
p-value0.3560.9320.5000.0860.381
SLC01C1R−0.700−0.2000.6000.500−0.700
p-value0.1880.7470.2850.3910.188
SLC02B1R−0.4910.5030.2550.223−0.503
p-value0.1500.1380.4760.5360.138
SLC04A1R0.1430.095−0.0480.4240.024
p-value0.7360.8230.9110.2950.955

Correlation between the expression of SLC transporters in Hoffa’s pad and clinical parameters

CRPWBCAge (years)Disease durationDAS28
SLC15A2r0.2560.250−0.3570.3820.255
p-value0.5790.5890.4320.3980.582
SLC22A18r−0.106−0.2610.2920.3440.085
p-value0.7700.4670.4130.3310.815
SLC16A3r0.4000.552−0.1950.3680.530
p-value0.2520.0980.5900.2950.115
SLC33A1r−0.0520.0170.3930.7030.286
p-value0.8940.9660.2950.0340.456
SLC19A1r−0.355−0.0240.3570.1940.217
p-value0.3880.9550.3850.6450.606
SLC47A1r0.4730.821−0.6430.2730.691
p-value0.2840.0230.1190.5540.086
SLC2A9r−0.279−0.2830.117−0.1770.185
p-value0.4680.4600.7650.6480.634
SLC51Ar0.5001.000−0.5000.8661.000
p-value0.667−0.6670.333−
SLC22A1r−0.866−0.5000.500−0.866−0.866
p-value0.3330.6670.6670.3330.333
SLC22A3r−0.540−0.6670.7330.203−0.445
p-value0.1340.0500.0250.6010.230
SLC7A5r0.5160.4860.2000.0880.530
p-value0.2950.3290.7040.8680.280
SLC22A4r−0.185−0.3570.8210.327−0.182
p-value0.6910.4320.0230.4740.696
SLC7A6r−0.256−0.1880.2130.4910.110
p-value0.4750.6030.5550.1500.763
SLC22A5r−0.669−0.2240.018−0.153−0.189
p-value0.0340.5330.9600.6720.601
SLC01C1r−0.906−0.2500.3930.255−0.436
p-value0.0050.5890.3830.5820.328
SLC02B1r−0.344−0.030−0.1880.436−0.268
p-value0.3310.9340.6020.2080.454
SLC04A1r0.7320.143−0.119−0.5900.395
p-value0.0390.7360.7790.1230.333

Antibodies used in the IHC procedure and the IRS evaluation

AntibodyHostManufacturerRate of dilutionTime of incubation/temperature
Anti-PEPT2 (SLC15A2)RabbitAbcam, Cambridge, United Kingdom1:751 h/RT
Anti-RFC1 (SLC19A1)MouseSanta Cruz Biotechnology Inc., Dallas, TX, USA1:1001 h/RT
Anti-MATE1 (SLC47A1)RabbitSigma Prestige, Merck, Darmstadt, Germany1:2001 h/RT

TaqMan gene expression assays

SLC transportersHousekeeping genes
Gene symbolTaqMan assay IDGene symbolTaqMan assay ID
SLC01A2Hs00366488_m1GUSBHs99999908_m1
SLC01B1Hs00272374_m1RPS9Hs02339424_g1
SLC01B3Hs00351987_m1
SLC01C1Hs00213714_m1
SLC02B1Hs01030353_m1
SLC04A1Hs00983988_m1
SLC04C1Hs00698884_m1
SLC10A1Hs00161820_m1
SLC10A2Hs01001557_m1
SLC15A1Hs00192639_m1
SLC15A2Hs01113665_m1
SLC16A3Hs00358829_m1
SLC19A1Hs00953344_m1
SLC22A1Hs00427552_m1
SLC22A11Hs00945829_m1
SLC22A12Hs00375985_m1
SLC22A18Hs00180039_m1
SLC22A2Hs01010726_m1
SLC22A3Hs00222691_m1
SLC22A4Hs01548718_m1
SLC22A5Hs00929869_m1
SLC22A6Hs00537914_m1
SLC22A7Hs00198527_m1
SLC22A8Hs00188599_m1
SLC22A9Hs00375768_m1
SLC28A1Hs00984403_m1
SLC28A2Hs00188407_m1
SLC2A9Hs00417125_m1
SLC33A1Hs00270469_m1
SLC47A1Hs00217320_m1
SLC47A2Hs00945650_m1
SLC51AHs00380895_m1
SLC51BHs01057182_m1
SLC7A5Hs01001183_m1
SLC7A6Hs00187727_m1

IRS values for transportation proteins expression in HFP in RA and OA patients

ProteinRAOA
MedianAverageMin.Max.MedianAverageMin.Max.
PEPT289.4741287.17212
RFC1129.0611244.93012
MATE187.4721286.5112
DOI: https://doi.org/10.2478/aite-2024-0014 | Journal eISSN: 1661-4917
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Language: English
Submitted on: Mar 5, 2024
Accepted on: May 13, 2024
Published on: Jun 27, 2024
Published by: Hirszfeld Institute of Immunology and Experimental Therapy
In partnership with: Paradigm Publishing Services
Publication frequency: 1 issue per year
Keywords:
Rheumatoid arthritis,
Synovial membrane,
SLC,
Drug transporters,
Hoffa’s pad
Related subjects:
Medicine,
Basic medical science,
Biochemistry,
Immunology,
Clinical medicine,
Clinical medicine, other,
Clinical chemistry

© 2024 Damian Malinowski, Katarzyna Piotrowska, Marek Droździk, Andrzej Pawlik, published by Hirszfeld Institute of Immunology and Experimental Therapy
This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 License.

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