title: Age-associated differences in transporter gene expression in kidneys of male rats.
abstract: Kidney transporters are involved in the secretion and reabsorption of endogenous and exogenous molecules. Numerous factors may influence their expression and affect drug disposition, efficacy and toxicity. The present study aimed to examine the development‑ and age‑associated variations in primary renal transporters in rats, including 6 uptake transporters: Organic anion transporter (OAT) 1 and 3, organic cation transporter (OCT) 1, 2 and 3 and organic anion‑transporting polypeptide (OATP) 4C1, and 6 efflux transporters: Multidrug resistance protein 1 (MDR1), breast cancer resistance protein (BCRP), multidrug resistance‑associated protein (MRP) 2 and 4, and multidrug and toxin extrusion protein (MATE) 1 and 2‑K. Kidneys from male Sprague Dawley rats during development (‑2, 1, 7, 14 and 21 days), maturation (28, 35 and 60 days) and aging (180, 540 and 850 days) were collected and total RNA was extracted, purified and subjected to reverse transcription‑quantitative polymerase chain reaction analysis. Total proteins were extracted for western blot analysis. OAT1 and 3, OCT1, BCRP, MRP2 and 4 and MATE2‑K expression levels were low in fetal kidneys, increased gradually following birth and markedly increased on maturation and adulthood. High levels were maintained until 850 days. OCT2, OATP4C1, Mdr1b and MATE1 expression levels were low in fetal kidneys, increased gradually following birth, and increased markedly on weaning, maturation and adulthood; however, levels were decreased on aging. OCT3 mRNA expression levels were low in fetal and newborn kidneys, and had two peaks at 35 and 850 days. The selected OAT1 and 3 and MDR1 protein expression levels revealed a similar expression pattern. Thus, kidney transporter expression is affected by ontogeny and aging, which may impact drug and toxicant disposition in children and the elderly.
authors.affiliation: Key Lab for Pharmacology of Ministry of Education, Zunyi Medical College, Zunyi, Guizhou 563000, P.R. China.
authors.forename: Yong-Ji
authors.initials: YJ
authors.lastname: Xu
authors.affiliation: Key Lab for Pharmacology of Ministry of Education, Zunyi Medical College, Zunyi, Guizhou 563000, P.R. China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Key Lab for Pharmacology of Ministry of Education, Zunyi Medical College, Zunyi, Guizhou 563000, P.R. China.
authors.forename: Yuan-Fu
authors.initials: YF
authors.lastname: Lu
authors.affiliation: Key Lab for Pharmacology of Ministry of Education, Zunyi Medical College, Zunyi, Guizhou 563000, P.R. China.
authors.forename: Shang-Fu
authors.initials: SF
authors.lastname: Xu
authors.affiliation: Key Lab for Pharmacology of Ministry of Education, Zunyi Medical College, Zunyi, Guizhou 563000, P.R. China.
authors.forename: Qin
authors.initials: Q
authors.lastname: Wu
authors.affiliation: Key Lab for Pharmacology of Ministry of Education, Zunyi Medical College, Zunyi, Guizhou 563000, P.R. China.
authors.forename: Jie
authors.initials: J
authors.lastname: Liu
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics; D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2 / Q000235:genetics*; D000375:Aging; D000818:Animals; D017920:Antiporters / Q000235:genetics; D005786:Gene Expression Regulation; D007668:Kidney / Q000254:growth & development / Q000502:physiology*; D008297:Male; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000235:genetics; D027362:Organic Anion Transport Protein 1 / Q000235:genetics; D027361:Organic Anion Transporters / Q000235:genetics*; D027701:Organic Cation Transport Proteins / Q000235:genetics*; D012333:RNA, Messenger / Q000032:analysis / Q000235:genetics; D017207:Rats, Sprague-Dawley
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D017920:Antiporters; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D027362:Organic Anion Transport Protein 1; D027361:Organic Anion Transporters; D027701:Organic Cation Transport Proteins; D012333:RNA, Messenger; C489249:Abcg2 protein, rat; C421043:Slc22a6 protein, rat; C515734:Slc47a1 protein, rat; C484531:organic anion transporting polypeptide 4C1, rat