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Hyaluronan And Proteoglycan Link Protein 1 (HAPLN1) promotes Proliferation and Pro-inflammatory phenotype but not mobility of Fibroblast-like Synoviocytes

ABSTRACT: Hyaluronan And Proteoglycan Link Protein 1 (HAPLN1) promotes Proliferation and Pro-inflammatory phenotype but not mobility of Fibroblast-like Synoviocytes

PROVIDER: PRJNA825502 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR18713535_1.fastq.gz	Fastqsanger.gz
	SRR18713535_2.fastq.gz	Fastqsanger.gz
	SRR18713536_1.fastq.gz	Fastqsanger.gz
	SRR18713536_2.fastq.gz	Fastqsanger.gz
	SRR18713537_1.fastq.gz	Fastqsanger.gz

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Project description:Periovulatory follicular matrix plays an important role in cumulus-oocyte complex (COC) expansion, ovulation, and luteal formation. Hyaluronan and proteoglycan link protein 1 (HAPLN1), a component of follicular matrix, was shown to enhance COC expansion in vitro. However, the regulatory mechanisms of periovulatory expression of Hapln1 and its role in periovulatory granulosa cells have not been elucidated. We first determined the periovulatory expression pattern of Hapln1 using pregnant mare serum gonadotropin/human chorionic gonadotropin (PMSG/hCG)-primed immature rat ovaries. Hapln1 expression was transiently induced both in intact ovaries and granulosa cells at 8 h and 12 h after hCG injection. This in vivo expression of Hapln1 was recapitulated by culturing preovulatory granulosa cells with hCG. The stimulatory effect of hCG was blocked by inhibition of protein kinase A, phosphatidylinositol-dependent kinase, p38 MAPK, epidermal growth factor signaling, and prostaglandin synthesis, revealing key mediators involved in LH-induced Hapln1 expression. In addition, knockdown of Runx1 and Runx2 expression by small interfering RNA or inhibition of RUNX activities by dominant-negative RUNX decreased hCG or agonist-induced Hapln1 expression. Chromatin immunoprecipitation assays verified the in vivo binding of RUNX1 and RUNX2 to the Hapln1 promoter in periovulatory granulosa cells. Luciferase reporter assays revealed that mutation of the RUNX binding sites completely obliterated the agonist-induced activity of the Hapln1 promoter. These data conclusively identified RUNX proteins as the crucial transcription regulators for LH-induced Hapln1 expression. Functionally, treatment with HAPLN1 increased the viability of cultured granulosa cells and decreased the number of the cells undergoing apoptosis, whereas knockdown of Hapln1 expression decreased granulosa cells viability. This novel finding indicates that HAPLN1 may promote periovulatory granulosa cell survival, which would facilitate their differentiation into luteal cells.

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Hyaluronan And Proteoglycan Link Protein 1 (HAPLN1) promotes Proliferation and Pro-inflammatory phenotype but not mobility of Fibroblast-like Synoviocytes

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