HPS proteins caused injury to the kidney in the Zebrafish

Mar 18, 2021

In this German study, attention was given to renal (kidney) disease in HPS. Zebrafish, which have similar genetic structures to humans, were used. Results showed that HPS proteins in certain types of HPS caused injury to the kidney in the Zebrafish. This study gives the HPS community an alert to monitor renal function with simple blood and urine tests. Medical treatment can slow the progression of the disease  if it should be present.

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  1. Sci Rep. 2019 Nov 27;9(1):17718. doi: 10.1038/s41598-019-54058-5.Characterizing renal involvement in Hermansky-Pudlak Syndrome in a zebrafish model.

    Schenk H(1)(2), Müller-Deile J(3)(4), Schroder P(5), Bolaños-Palmieri P(3)(4), Beverly-Staggs L(5), White R(5), Bräsen JH(6), Haller H(3)(5), Schiffer M(7)(8).

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Author information: (1) Department of Medicine/Nephrology, Hannover Medical School, 30625, Hannover, Germany. Schenk.Heiko@mh-hannover.de. (2) Mount Desert Island Biological Laboratory, Salisbury Cove, ME, 04672, USA. Schenk.Heiko@mh-hannover.de. (3) Department of Medicine/Nephrology, Hannover Medical School, 30625, Hannover, Germany. (4) Department of Nephrology and Hypertension, University of Erlangen-Nurnberg, Erlangen, Germany. (5) Mount Desert Island Biological Laboratory, Salisbury Cove, ME, 04672, USA. (6) Institute of Pathology, Nephropathology Unit, Hannover Medical School, Hannover, Germany. (7) Department of Medicine/Nephrology, Hannover Medical School, 30625, Hannover, Germany. Mario.Schiffer@uk-erlangen.de. (8) Department of Nephrology and Hypertension, University of Erlangen-Nurnberg, Erlangen, Germany. Mario.Schiffer@uk-erlangen.de.

Hermansky-Pudlak Syndrome (HPS) is a rare disease caused by mutations in the genes coding for various HPS proteins. HPS proteins are part of multi-subunit complexes involved in the biogenesis of organelles from the lysosomal-endosomal-system. In humans, this syndrome is characterized by the presence of albinism, platelet dysfunction and pulmonary fibrosis. The renal component to the disease remains unstudied and untreated in patients with HPS. Here we demonstrate that in humans, HPS proteins have a high renal expression with active transcription of HPS1, 3, 4 and 5 in human podocyte cell culture, suggesting that impaired function of HPS proteins could directly impact renal function. Therefore, we developed a zebrafish model to study the renal involvement of HPS proteins in proteinuric kidney disease. Remarkably, knockdown of HPS genes in zebrafish causes glomerular injury with edema, proteinuria and structural changes of the glomerular filtration barrier. Moreover, reduced expression of HPS proteins in zebrafish recapitulates other important disease hallmarks, like hypopigmentation and accumulation of intracellular debris characteristic of lysosomal disorders. In conclusion, we present a valid zebrafish model that highlights the previously underestimated relevance of renal disease in HPS. This draws attention to the therapeutic options available to manage this component of the syndrome.

DOI: 10.1038/s41598-019-54058-5 PMCID: PMC6881439 PMID: 31776394 [Indexed for MEDLINE]

Conflict of interest statement: The authors declare no competing interests.