Our major research interest is investigating the regulation of ion transport in epithelial tissues of the kidney and airway. We have particular expertise studying the epithelial sodium channel (ENaC) and its regulation by trafficking and recycling. Studies focus on two tissues, the distal kidney nephron where upregulation of the channel is associated with volume expansion and hypertension, and human airway where ENaC hyperactivity is linked to cystic fibrosis. The main focus is understanding the cellular regulation of these sodium transporters and channels. The research could therefore be classified as cell physiology.
Our current work investigates how distal nephron transporters respond to a variety of signals including hormonal regulation via microRNAs. We have identified a subset of microRNAs that are specifically regulated by steroid hormones (aldosterone) and demonstrated that changes in microRNA expression directly alters sodium transport in the kidney. We use a range of techniques to investigate the effect of aldosterone on miRNA regulation in the kidney, and identify new protein targets that regulate ENaC. In ongoing work we have expanded this analysis to incorporate a number of hormonal signals in the kidney including vasopressin, insulin and related steroid hormones. Our lab uses a range of techniques to address these questions including RNA-Seq (microRNA deep-seq), genomic and proteomic analysis, in vitro and in vivo knockout studies, electrophysiological recordings of ion transport, biochemical and imaging approaches to study protein regulation and trafficking and mouse metabolic and diet studies.
- Butterworth MB. Non-coding RNAs and the mineralocorticoid receptor in the kidney.. Mol Cell Endocrinol. 2021 Feb 5;521():111115. doi: 10.1016/j.mce.2020.111115. PubMed PMID: 33301840;
- Butterworth MB, Alvarez de la Rosa D. Regulation of Aldosterone Signaling by MicroRNAs.. Vitam Horm. 2019;109():69-103. doi: 10.1016/bs.vh.2018.09.002. PubMed PMID: 30678867;
- Klemens CA, Edinger RS, Kightlinger L, Liu X, Butterworth MB. Ankyrin G Expression Regulates Apical Delivery of the Epithelial Sodium Channel (ENaC).. J Biol Chem. 2017 Jan 6;292(1):375-385. doi: 10.1074/jbc.M116.753616. PubMed PMID: 27895120;
- Liu X, Edinger RS, Klemens CA, Phua YL, Bodnar AJ, LaFramboise WA, Ho J, Butterworth MB. A MicroRNA Cluster miR-23-24-27 Is Upregulated by Aldosterone in the Distal Kidney Nephron Where it Alters Sodium Transport.. J Cell Physiol. 2017 Jun;232(6):1306-1317. doi: 10.1002/jcp.25599. PubMed PMID: 27636893;