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Collagen formation, function and role in kidney disease

Nature Reviews Nephrology volume 21, pages 200–215 (2025)Cite this article

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Abstract

Highly abundant in mammals, collagens define the organization of tissues and participate in cell signalling. Most of the 28 vertebrate collagens, with the exception of collagens VI, VII, XXVI and XXVIII, can be categorized into five subgroups: fibrillar collagens, network-forming collagens, fibril-associated collagens with interrupted triple helices, membrane-associated collagens with interrupted triple helices and multiple triple-helix domains with interruptions. Collagen peptides are synthesized from the ribosome and enter the rough endoplasmic reticulum, where they undergo numerous post-translational modifications. The collagen chains form triple helices that can be secreted to form a diverse array of supramolecular structures in the extracellular matrix. Collagens are ubiquitously expressed and have been linked to a broad spectrum of disorders, including genetic disorders with kidney phenotypes. They also have an important role in kidney fibrosis and mass spectrometry-based proteomic studies have improved understanding of the composition of fibrosis in kidney disease. A wide range of therapeutics are in development for collagen and kidney disorders, including genetic approaches, chaperone therapies, protein degradation strategies and anti-fibrotic therapies. Improved understanding of collagens and their role in disease is needed to facilitate the development of more specific treatments for collagen and kidney disorders.

Key points

  • Collagens are highly abundant in vertebrates and have critical roles in structural integrity, tissue organization and signalling.

  • Collagens undergo a series of processing events that begin with trafficking into the rough endoplasmic reticulum and post-translational modification.

  • Pathogenic variants in collagen genes are associated with a spectrum of disorders.

  • In the kidney, collagen variants cause Alport syndrome, congenital abnormalities of the kidney and urinary tract and the multisystem disorder, Gould syndrome.

  • Dysregulated collagens are also a hallmark of fibrosis, which is a major cause of organ failure.

  • Current and future therapies for collagen disorders and kidney diseases can be broadly categorized as genetic approaches, chaperone therapies, protein degradation strategies and anti-fibrotic therapies.

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Fig. 1: The collagen family of proteins.
Fig. 2: Collagens in the human kidney.
Fig. 3: Approaches to treating collagen disorders and fibrosis in the kidney.

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Acknowledgements

The authors thank Alport UK and The Alport Syndrome Foundation for their support. V.D.G.’s research has been supported by a Canada Graduate Scholarship — Master’s from the Canadian Institutes of Health Research (CIHR). M.B.’s research has been supported by the Canadian Institutes of Health Research (175145, 173378), Toronto General Research Institute and Toronto General Hospital Foundation. R.L.’s research is supported by the Wellcome Trust (202860/Z/16/Z), Kidney Research UK and The Stoneygate Trust.

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  1. These authors contributed equally: Moumita Barua, Rachel Lennon.

Authors and Affiliations

  1. Institute of Medical Science, University of Toronto, Toronto, Ontario, Canada

    Vanessa De Gregorio & Moumita Barua

  2. Toronto General Hospital Research Institute, Toronto, Ontario, Canada

    Vanessa De Gregorio & Moumita Barua

  3. Division of Nephrology, University Health Network, Toronto, Ontario, Canada

    Moumita Barua

  4. Department of Medicine, University of Toronto, Toronto, Ontario, Canada

    Moumita Barua

  5. Wellcome Centre for Cell-Matrix Research, Faculty of Biology, Medicine and Health, University of Manchester, Manchester, UK

    Rachel Lennon

  6. Department of Paediatric Nephrology, Royal Manchester Children’s Hospital, Manchester, UK

    Rachel Lennon

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De Gregorio, V., Barua, M. & Lennon, R. Collagen formation, function and role in kidney disease. Nat Rev Nephrol 21, 200–215 (2025). https://doi.org/10.1038/s41581-024-00902-5

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