司坦尼氏降鈣素對青鱂魚的胰島素樣生長因子訊號之影響

司坦尼氏降鈣素 (Stanniocalcin, STC) 是脊椎動物中的降鈣賀爾蒙。當魚類處於高鈣環境時，stanniocalcin-1 (stc-1) 表現量會增加，而表皮鈣離子通道蛋白 (Epithelial calcium channel, ECaC) 則會減少，以降低魚類對鈣離子的吸收，但其中的調節機制尚不清楚。另一方面，stanniocalcin-2 (stc-2) 能夠透過阻斷妊娠相關血漿蛋白A (pregnancy-associated plasma protein A, PAPP-A) 的蛋白水解活性來抑制胰島素樣生長因子結合蛋白4 (insulin-like growth factor binding protein 4, IGFBP-4) 釋放 IGF 配體。此外，已知IGF 訊號在急性海水適應後會調節轉運蛋白的表現和離子細胞的形態，因此，本研究旨在探討 STC 是否會透過 IGF 訊息傳遞的路徑而影響鈣離子的調節。組織分佈分析顯示，青鱂魚的stc亞型在鰓中均有表現。原位雜合與免疫染色顯示stanniocalcin-1like (stc-1like) 在受精後六天的青鱂魚胚胎中的司坦尼氏小體 (corpuscles of Stannius, CS) 中表現。在高鈣適應後，青鱂魚胚胎中的stc-1like mRNA顯著增加；低鈣適應後鰓中的stc-1、stc-2、igf1、igf1ra和igf1rb mRNA顯著降低，papp-aa、igfbp5a和trpv6 mRNA顯著增加。藥理實驗發現，阻斷IGF受體不僅降低stc-1like和igfra mRNA的表現量，也降低ECaC離子細胞對鈣離子的吸收。結果表明，STCs確實以全身或局部調節的方式參與印度青鱂魚的鈣離子平衡，可能是透過IGF訊號傳導，但詳細的機制仍有待進一步研究。

關鍵字

鈣吸收；印度青鱂魚；胰島素樣生長因子；離子調節；司坦尼氏降鈣素

並列摘要

Stanniocalcin (STC) is a hypocalcemic hormone in vertebrates. In teleosts, the mRNA expression of stanniocalcin-1 (stc-1) increases while the expression of epithelial calcium channel (ECaC) decreases under high-Ca2+ environments for reducing Ca2+ uptake; however, the regulating mechanism is as yet unclear. On the other hand, stanniocalcin-2 (stc-2) is able to suppress insulin-like growth factor binding protein 4 (IGFBP-4) to release the IGF ligand via blocking the proteolytic activity of pregnancy associated plasma protein A (PAPP-A). Moreover, IGF signaling is also known to regulate the expression of transporters and the morphology of ionocytes after acute seawater acclimation. Thus, the present study aims to investigate whether STC affects the regulation of Ca2+ through IGF signaling pathways. Tissue distribution analysis showed all stc isoforms expressed in the Indian medaka gill. In situ hybridization and immunostaining exhibited the expression of stanniocalcin-1like (stc-1like) in corpuscles of Stannius (CS) in 6 days post fertilization (dpf) Indian medaka embryos. After high-Ca2+ acclimation, stc-1like mRNA expression increased significantly in Indian medaka embryos; stc-1, stc-2, igf1, igf1ra, and igf1rb expression significantly decreased and papp-aa, igfbp5a, and trpv6 expression significantly increased in gills after low-Ca2+ acclimation. Pharmacological experiments found that the blockage of the IGF receptor not only decreased stc-1like and igfra mRNA expression but also decreased the Ca²+ uptake of the ECaC ionocytes. These results suggest that STCs are involved in the Ca²+ homeostasis of Indian medaka in a global or local regulatory manner, probably through IGF signaling, but the detailed mechanism still needs further investigation.

並列關鍵字

calcium uptake ； Indian medaka ； insulin-like growth factor ； ion regulation ； stanniocalcin

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