Pro-fibrotic Phenotype of Human Hermansky-Pudlak Syndrome (HPS) Fibroblasts

Authors

• CH Han
• T Yokoyama
• BR Gochuico
• MCV Malicdan
• WA Gahl

Abstract

Hermansky-Pudlak syndrome (HPS) is a rare autosomal recessive disorder characterized by abnormal biogenesis of lysosome-related organelles such as melanosomes and platelet delta granules, resulting in oculocutaneous albinism and a bleeding diathesis. There are 9 known HPS-causing genes, each encoding a protein that, in combination with other proteins, function to form or traffic lysosome-related organelles. Some individuals with HPS develop breathing problems due to pulmonary fibrosis, and usually appear during an individual's early thirties and rapidly worsen. Types 1, 2, and 4 are the only types associated with pulmonary fibrosis. Though there are currently no clinical instances of pulmonary fibrosis development in HPS subtypes 3, 5 or 9, such cases may just not have been observed yet as many patients tend to be very young. In fact, only recently has mild pulmonary fibrosis been observed in an older HPS 5 patient. Therefore, for this study, we looked at how dermal and lung fibroblasts (FB) of different HPS subtypes phenotypically compared to wild type (WT). We decided to study a variety of different extracellular matrix (ECM) proteins and ECM related proteins through gene expression and protein levels. FBs used in the study were analyzed with and without stimulation with Transforming Growth Factor Beta-1 (TGFß-1) and Galectin-3 to see if the HPS subtypes had pro-fibrotic tendencies. We hypothesize that FBs of certain HPS subtypes would show gene expression and protein levels that suggest them to be pro-fibrotic, and would match the other clinical features for each of the different HPS subtypes.

Scientific Focus Area: Genetics and Genomics

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