+1 Recommend
2 collections
      Call for Papers in Digital Biomarkers: The State of Digital Biomarkers and Mental Health

      Extended Submission Deadline: January 31, 2024 

      Submit now

      Call for Papers in Kidney and Blood Pressure ResearchKidney Function and Omics Science

      Submission Deadline: December 20, 2023

      Submit now

      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      Phase Separation in Kidney Diseases: Autosomal Dominant Polycystic Kidney Disease and Beyond


      Read this article at

          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.



          The formation of biomolecular condensates via phase separation has emerged as a fundamental principle underlying the spatiotemporal coordination of biological activities in cells. Aberrant biomolecular condensates often directly regulate key cellular process involved in the pathogenesis of human diseases, including kidney diseases.


          In this review, we summarize the physiological roles of phase separation and methodologies for phase separation studies. Taking autosomal dominant polycystic kidney disease as an example, we discuss recent advances toward elucidating the multiple mechanisms involved in kidney pathology arising from aberrant phase separation. We suggest that dysregulation of phase separation contributes to the pathogenesis of other important kidney diseases, including kidney injury and fibrosis.

          Key Messages

          Phase separation provides a useful new concept to understand the mechanisms underlying kidney disease development. Targeting aberrant phase-separated condensates offers new therapeutic avenues for combating kidney diseases.

          Related collections

          Most cited references63

          • Record: found
          • Abstract: found
          • Article: not found

          Liquid-liquid phase separation in biology.

          Cells organize many of their biochemical reactions in non-membrane compartments. Recent evidence has shown that many of these compartments are liquids that form by phase separation from the cytoplasm. Here we discuss the basic physical concepts necessary to understand the consequences of liquid-like states for biological functions.
            • Record: found
            • Abstract: found
            • Article: not found

            Coactivator condensation at super-enhancers links phase separation and gene control

            Super-enhancers (SEs) are clusters of enhancers that cooperatively assemble a high density of transcriptional apparatus to drive robust expression of genes with prominent roles in cell identity. Here, we demonstrate that the SE-enriched transcriptional coactivators BRD4 and MED1 form nuclear puncta at SEs that exhibit properties of liquid-like condensates and are disrupted by chemicals that perturb condensates. The intrinsically disordered regions (IDRs) of BRD4 and MED1 can form phase-separated droplets and MED1-IDR droplets can compartmentalize and concentrate transcription apparatus from nuclear extracts. These results support the idea that coactivators form phase-separated condensates at SEs that compartmentalize and concentrate the transcription apparatus, suggest a role for coactivator IDRs in this process, and offer insights into mechanisms involved in control of key cell identity genes.
              • Record: found
              • Abstract: found
              • Article: not found

              A Liquid-to-Solid Phase Transition of the ALS Protein FUS Accelerated by Disease Mutation.

              Many proteins contain disordered regions of low-sequence complexity, which cause aging-associated diseases because they are prone to aggregate. Here, we study FUS, a prion-like protein containing intrinsically disordered domains associated with the neurodegenerative disease ALS. We show that, in cells, FUS forms liquid compartments at sites of DNA damage and in the cytoplasm upon stress. We confirm this by reconstituting liquid FUS compartments in vitro. Using an in vitro "aging" experiment, we demonstrate that liquid droplets of FUS protein convert with time from a liquid to an aggregated state, and this conversion is accelerated by patient-derived mutations. We conclude that the physiological role of FUS requires forming dynamic liquid-like compartments. We propose that liquid-like compartments carry the trade-off between functionality and risk of aggregation and that aberrant phase transitions within liquid-like compartments lie at the heart of ALS and, presumably, other age-related diseases.

                Author and article information

                Kidney Dis (Basel)
                Kidney Dis (Basel)
                Kidney Diseases
                S. Karger AG (Basel, Switzerland )
                25 May 2023
                August 2023
                : 9
                : 4
                : 229-238
                [a ]Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Tianjin Institute of Urology, Key Laboratory of Immune Microenvironment and Disease (Ministry of Education), The Province and Ministry Co-sponsored Collaborative Innovation Center for Medical Epigenetics, The Second Hospital of Tianjin Medical University, Tianjin Medical University, Tianjin, China
                [b ]Division of Nephrology, State Key Laboratory of Organ Failure Research, National Clinical Research Center of Kidney Disease, Guangdong Provincial Institute of Nephrology, Guangdong Provincial Key Laboratory of Renal Failure Research, Nanfang Hospital, Southern Medical University, Guangzhou, China
                Author notes
                Correspondence to: Jing Nie, niejing@ 123456smu.edu.cn Yupeng Chen, ychen@ 123456tmu.edu.cn
                © 2023 The Author(s). Published by S. Karger AG, Basel

                This article is licensed under the Creative Commons Attribution-NonCommercial 4.0 International License (CC BY-NC) ( http://www.karger.com/Services/OpenAccessLicense). Usage and distribution for commercial purposes requires written permission.

                : 27 December 2022
                : 15 March 2023
                : 2023
                Page count
                Figures: 3, References: 63, Pages: 10
                This study was supported by the Natural Science Foundation of Tianjin (19JCJQJC63800 to Y.C., 21JCJQJC00100 to L.Z.).
                Review Article

                phase separation,autosomal dominant polycystic kidney disease,metabolism,epigenetics,kidney diseases


                Comment on this article