Bpifcl modulates kiss2 expression under the influence of 11-ketotestosterone in female zebrafish

Abstract

The bactericidal/permeability-increasing (BPI) fold-containing (BPIF) superfamily of genes expressed in the brain are purportedly involved in modulating brain function in response to stress, such as inflammation. Kisspeptin, encoded by kiss, is affected by inflammation in the brain; therefore, BPIF family genes might be involved in the modulation of kisspeptin in the brain. In this study, we investigated the expression of BPIF family C, like (bpifcl) in zebrafish brain and its involvement in kiss2 regulation. The identified, full-length sequence of a bpifcl isoform expressed in the zebrafish brain contained the BPI fold shared by BPIF family members. bpifcl mRNA expression in female zebrafish brains was significantly higher than that in males. Exposure of female zebrafish to 11-ketotestosterone decreased bpifcl and kiss2 mRNA expression. bpifcl knockdown by bpifcl-specific small interfering RNA administration to female zebrafish brain decreased kiss2 mRNA expression. bpifcl expression was widely distributed in the brain, including in the dorsal zone of the periventricular hypothalamus (Hd). Furthermore, bpifcl was also expressed in KISS2 neurons in the Hd. These results suggest that the Bpifcl modulates kiss2 mRNA expression under the influence of testosterone in the Hd of female zebrafish.The bactericidal/permeability-increasing (BPI) fold-containing (BPIF) superfamily of genes is functionally classified into five groups: palate, lung and nasal epithelium clone (PLUNC); lipopolysaccharide-binding protein (LBP); BPI protein; phospholipid transfer protein (PLTP); cholesterol ester transfer protein (CETP) 1, 2 . All BPIF family members share the BPI fold, which has an elongated, boomerang shape consisting of two distinct N-and C-terminal domain barrels with a highly similar secondary structure 3 . Both domains consist of two twisted, anti-parallel β-sheets and two α-helices, with both domains connected to each other by a β-sheet 4 .BPIF family of genes are expressed in a wide range of vertebrates 5 and mainly involved in the innate immune system and lipoprotein metabolism. BPI and LBP are plasma proteins that play an important role in the innate immune system against invading pathogens owing to a high affinity for the lipopolysaccharides of Gram-negative bacteria 3,6 . PLUNC proteins are suggested to be host defence molecules because their expression alters in response to inflammation caused by smoking, chemical irritants, and infection 7,8 . CETP and PLTP are both plasma proteins that play an important role in lipoprotein metabolism 9,10 . Recently, the expression of BPIF family of genes has been reported in the brain 11 . We have also reported the expression of BPIF family of genes, such as bpifa1, gm1006 and rya3 in the mouse brain, particularly in the preoptic area 12 . The expression of these genes decreases with age. Because ageing causes oxidative stress and inflammation in the brain 13 , the identified BPIF family of genes might respond to oxidative stress and inflammation similar to the PLUNC protein grou...

Transcriptomic signatures associated with underlying rapid changes in the early phase brain of bi-directional sex change in Trimma okinawae

“…gonads of female and male-like female) in T. okinawae (electronic supplementary material, table S9). A previous study using Zebrafish revealed that this gene modulates the expression of kiss2 , an orthologous gene regulating reproductive development through GnRH neuronal activity in mammals [37]. Interestingly, kisspeptin may have other neuroendocrinal functions on social and sexual behaviour by regulating neurons that express isotocin and vasotocin, although it is not a direct regulator of reproduction through GnRH neurons in several fish species [38–40].…”

Novel heterozygous BPIFC variant in a Chinese pedigree with hereditary trichilemmal cysts

“…BPIFC protein is mainly expressed in human epidermis (Toulza et al, ) and highly expressed in the basal layer of the epidermis from inflammatory skin of patients with psoriasis (Mulero et al, ). In zebrafish, BPIF family C, like ( bpifcl ) modulates the expression of Kisspeptin that a molecule known to be affected by inflammation in the brain (Moriya, Tahsin, & Parhar, ). Comparison of the mouse and human orthologs showed that BPIFC protein is evolving rapidly, having an elevated Ka/Ks ratio similar to the PLUNC protein family and BPI protein (Bingle et al, ), which implies that BPIFC protein is involved in host defense.…”