Browsing by Author "Fang, Jing"

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    G protein-coupled receptor 68 increases the number of B lymphocytes
    (e-Century Publishing, 2020-04-15) He, Xiaofei; Feng, Saran; Hawkins, Caleb; Lawley, Lauren; Fan, Wenxin; Xu, Yan; Zha, Xiang-Ming; Fang, Jing; Obstetrics and Gynecology, School of Medicine
    G protein-coupled receptor 68 (GPR68) is a proton sensor that is activated upon binding to extracellular protons. We have previously found that GPR68 induces a proapoptotic pathway in bone marrow (BM) cells from the patients with myelodysplastic syndromes (MDS) after treated with lenalidomide. However, the function of GPR68 in normal hematopoietic cells remains unclear. With genetic loss of function approach, we found reduced frequency and number of B lymphocytes in the peripheral blood (PB) of whole body Gpr68-/- mice compared to control littermates upon aging. During hematopoietic regeneration, such as in response to fluorouracil (5-FU), we also found reduced frequency and number of B lymphocytes in Gpr68-/- mice compared to wild type mice. Mechanism studies revealed that Gpr68 expression was upregulated in B lymphocytes of BM during aging and in hematopoietic progenitor cells after treatment with 5-FU. In addition, activation of Gpr68 by its activators increased the frequency and number of B lymphocytes. Our studies indicate that Gpr68 expression is upregulated in hematopoietic cells upon aging and during hematopoietic regeneration that ends up with increased number of B lymphocytes.
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    Whole body deletion of Gpr68 does not change hematopoietic stem cell function
    (Elsevier, 2020-06-20) He, Xiaofei; Hawkins, Caleb; Lawley, Lauren; Freeman, Kennedy; Phan, Tra Mi; Zhang, Jiajia; Xu, Yan; Fang, Jing; Obstetrics and Gynecology, School of Medicine
    G protein-coupled receptor 68 (GPR68) responds to extracellular protons, thus called the proton-sensing G protein-coupled receptor (GPCR), leading to activation of the phospholipase C-β (PLCβ)/calcium (Ca2+) pathway or the adenylyl cyclase (AC)/cyclic AMP (cAMP) pathway. We recently found that whole body deletion of Gpr68 (Gpr68-/- mice) reduced the number of B lymphocytes with age and during hematopoietic regeneration, such as in response to fluorouracil (5-FU) administration. This prompted us to characterize the hematopoietic stem cell (HSC) phenotype in Gpr68-/- mice. Despite high level of Gpr68 protein expression on HSC in bone marrow (BM), the pool size of HSC was unaltered in Gpr68-/- mice either under steady state or upon stress, including aging and 5-FU treatment. HSC from Gpr68-/- mice exhibited comparable cellular features, such as cell cycle quiescence and cell survival. HSC from Gpr68-/- mice also exhibited comparable competitiveness after serial transplantation. Surprisingly, cytosolic Ca2+ accumulation was increased in HSC from Gpr68-/- mice. In contrast, cAMP levels were reduced in hematopoietic stem and progenitor cells (HSPC) from Gpr68-/- mice. Intriguingly, we found high level of Gpr68 protein expression on non-hematopoietic cells in BM, especially endothelial cells that function as HSC niche. In addition, expression of other proton-sensing GPCR was upregulated in HSPC from Gpr68-/- mice. Our studies suggest that Gpr68-/- mice display insignificant phenotype on HSC biology, possibly due to the function of Gpr68 in non-hematopoietic cells and/or the compensatory effects from other proton-sensing GPCR.