Browsing by Author "Wang, Honghui"

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    Diversity and Complexity of the Large Surface Protein Family in the Compacted Genomes of Multiple Pneumocystis Species
    (American Society for Microbiology, 2020-03-03) Ma, Liang; Chen, Zehua; Huang, Da Wei; Cissé, Ousmane H.; Rothenburger, Jamie L.; Latinne, Alice; Bishop, Lisa; Blair, Robert; Brenchley, Jason M.; Chabé, Magali; Deng, Xilong; Hirsch, Vanessa; Keesler, Rebekah; Kutty, Geetha; Liu, Yueqin; Margolis, Daniel; Morand, Serge; Pahar, Bapi; Peng, Li; Van Rompay, Koen K.A.; Song, Xiaohong; Song, Jun; Sukura, Antti; Thapar, Sabrina; Wang, Honghui; Weissenbacher-Lang, Christiane; Xu, Jie; Lee, Chao-Hung; Jardine, Claire; Lempicki, Richard A.; Cushion, Melanie T.; Cuomo, Christina A.; Kovacs, Joseph A.; Pathology and Laboratory Medicine, School of Medicine
    Pneumocystis, a major opportunistic pathogen in patients with a broad range of immunodeficiencies, contains abundant surface proteins encoded by a multicopy gene family, termed the major surface glycoprotein (Msg) gene superfamily. This superfamily has been identified in all Pneumocystis species characterized to date, highlighting its important role in Pneumocystis biology. In this report, through a comprehensive and in-depth characterization of 459 msg genes from 7 Pneumocystis species, we demonstrate, for the first time, the phylogeny and evolution of conserved domains in Msg proteins and provide a detailed description of the classification, unique characteristics, and phylogenetic relatedness of five Msg families. We further describe, for the first time, the relative expression levels of individual msg families in two rodent Pneumocystis species, the substantial variability of the msg repertoires in P. carinii from laboratory and wild rats, and the distinct features of the expression site for the classic msg genes in Pneumocystis from 8 mammalian host species. Our analysis suggests multiple functions for this superfamily rather than just conferring antigenic variation to allow immune evasion as previously believed. This study provides a rich source of information that lays the foundation for the continued experimental exploration of the functions of the Msg superfamily in Pneumocystis biology.
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    Fibroblast GATA-4 and GATA-6 promote myocardial adaptation to pressure overload by enhancing cardiac angiogenesis
    (Springer, 2021-04-19) Dittrich, Gesine M.; Froese, Natali; Wang, Xue; Kroeger, Hannah; Wang, Honghui; Szaroszyk, Malgorzata; Malek‑Mohammadi, Mona; Cordero, Julio; Keles, Merve; Korf‑Klingebiel, Mortimer; Wollert, Kai C.; Geffers, Robert; Mayr, Manuel; Conway, Simon J.; Dobreva, Gergana; Bauersachs, Johann; Heineke, Joerg; Pediatrics, School of Medicine
    Heart failure due to high blood pressure or ischemic injury remains a major problem for millions of patients worldwide. Despite enormous advances in deciphering the molecular mechanisms underlying heart failure progression, the cell-type specific adaptations and especially intercellular signaling remain poorly understood. Cardiac fibroblasts express high levels of cardiogenic transcription factors such as GATA-4 and GATA-6, but their role in fibroblasts during stress is not known. Here, we show that fibroblast GATA-4 and GATA-6 promote adaptive remodeling in pressure overload induced cardiac hypertrophy. Using a mouse model with specific single or double deletion of Gata4 and Gata6 in stress activated fibroblasts, we found a reduced myocardial capillarization in mice with Gata4/6 double deletion following pressure overload, while single deletion of Gata4 or Gata6 had no effect. Importantly, we confirmed the reduced angiogenic response using an in vitro co-culture system with Gata4/6 deleted cardiac fibroblasts and endothelial cells. A comprehensive RNA-sequencing analysis revealed an upregulation of anti-angiogenic genes upon Gata4/6 deletion in fibroblasts, and siRNA mediated downregulation of these genes restored endothelial cell growth. In conclusion, we identified a novel role for the cardiogenic transcription factors GATA-4 and GATA-6 in heart fibroblasts, where both proteins act in concert to promote myocardial capillarization and heart function by directing intercellular crosstalk.