title: Inhibition of NF-κB promotes autophagy via JNK signaling pathway in porcine granulosa cells.
abstract: The transcription factor nuclear factor-κB (NF-κB) plays an important role in diverse processes, including cell proliferation and differentiation, apoptosis and inflammation. However, the role of NF-κB in porcine follicle development is not clearly elucidated. In this study, we demonstrated that follicle stimulating hormone (FSH) increased the level of inhibitor of NF-κB (IκB) protein and promoted the cytoplasmic localization of p65, indicating that FSH inhibits the activation of NF-κB in porcine granulosa cells. Moreover, inhibition of NF-κB by FSH or another specific inhibitor of NF-κB, pyrrolidine dithiocarbamate (PDTC), could activate JNK signaling and enhance autophagic activity in porcine granulosa cells. Knockdown of RelA (p65) Subunit of NF-κB by RNA interference abrogated the activation of JNK signaling pathway and the increase of autophagic protein expression by FSH. Meanwhile, the functional signiﬁcance of FSH or PDTC-mediated autophagy were further investigated. Our results demonstrated that the increased autophagy promoted progesterone secretion in porcine granulosa cells. Blockage of autophagy by chloroquine obviated the FSH or PDTC-induced progesterone production. Taken together, these results indicate that inhibition of NF-κB increased autophagy via JNK signaling, and promote steroidogenesis in porcine granulosa cells. Our results provide new insights into the regulation and function of autophagy in mammalian follicle development.
authors.affiliation: Laboratory of Animal Embryonic Biotechnology, College of Animal Science and Technology, China Agricultural University, Beijing 100193, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Gao
authors.affiliation: Laboratory of Animal Embryonic Biotechnology, College of Animal Science and Technology, China Agricultural University, Beijing 100193, China.
authors.forename: Lu
authors.initials: L
authors.lastname: Lin
authors.affiliation: Laboratory of Animal Embryonic Biotechnology, College of Animal Science and Technology, China Agricultural University, Beijing 100193, China.
authors.forename: Ihtesham Ul
authors.initials: IU
authors.lastname: Haq
authors.affiliation: Laboratory of Animal Embryonic Biotechnology, College of Animal Science and Technology, China Agricultural University, Beijing 100193, China. Electronic address: zengshenming@gmail.com.
authors.forename: Shen-Ming
authors.initials: SM
authors.lastname: Zeng
mesh_terms: D000818:Animals; D017209:Apoptosis; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism*; D001343:Autophagy; D002467:Cell Nucleus / Q000378:metabolism; D049109:Cell Proliferation; D003593:Cytoplasm / Q000378:metabolism; D005260:Female; D005640:Follicle Stimulating Hormone / Q000378:metabolism; D006107:Granulosa Cells / Q000378:metabolism*; D020287:In Situ Nick-End Labeling; D048670:MAP Kinase Kinase 4 / Q000378:metabolism*; D008856:Microscopy, Fluorescence; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000378:metabolism*; D006080:Ovarian Follicle / Q000378:metabolism; D011374:Progesterone / Q000737:chemistry; D011759:Pyrrolidines / Q000737:chemistry; D015398:Signal Transduction; D013552:Swine; D013859:Thiocarbamates / Q000737:chemistry; D051996:Transcription Factor RelA / Q000378:metabolism
chemical_list: D051017:Apoptosis Regulatory Proteins; D016328:NF-kappa B; D011759:Pyrrolidines; D013859:Thiocarbamates; D051996:Transcription Factor RelA; C020972:pyrrolidine dithiocarbamic acid; D011374:Progesterone; D005640:Follicle Stimulating Hormone; D048670:MAP Kinase Kinase 4
keywords: Autophagy; FSH; JNK; NF-κB; Porcine; c-Jun