CD147 regulates extrinsic apoptosis in spermatocytes by modulating NFκB signaling pathways

// Chaoqun Wang 1 , Kin Lam Fok 1 , Zhiming Cai 2 , Hao Chen 1, 2 , Hsiao Chang Chan 1, 3 1 Epithelial Cell Biology Research Center, Key Laboratory for Regenerative Medicine of The Ministry of Education of China, School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, Hong Kong 2 Department of Gynecology, The Second People's Hospital of Shenzhen, Shenzhen, PR China 3 Sichuan University – The Chinese University of Hong Kong Joint Laboratory for Reproductive Medicine, West China Second University Hospital, Sichuan University, Chengdu, China Correspondence to: Hsiao Chang Chan, email: hsiaocchan@cuhk.edu.hk Hao Chen, email: chenhaojob@yahoo.com Keywords: CD147, non-canonical NFκB, apoptosis, spermatocytes, spermatogenesis Received: June 29, 2016      Accepted: October 19, 2016      Published: November 25, 2016 ABSTRACT CD147 null mutant male mice are infertile with arrested spermatogenesis and increased apoptotic germ cells. Our previous studies have shown that CD147 prevents apoptosis in mouse spermatocytes but not spermatogonia. However, the underlying mechanism remains elusive. In the present study, we aim to determine the CD147-regulated apoptotic pathway in mouse spermatocytes. Our results showed that immunodepletion of CD147 triggered apoptosis through extrinsic apoptotic pathway in mouse testis and spermatocyte cell line (GC-2 cells), accompanied by activation of non-canonical NFκB signaling and suppression of canonical NFκB signaling. Furthermore, CD147 was found to interact with TRAF2, a factor known to regulate NFκB and extrinsic apoptotic signaling, and interfering CD147 led to the decrease of TRAF2. Consistently, depletion of CD147 by CRISPR/Cas9 technique in GC-2 cells down-regulated TRAF2 and resulted in cell death with suppressed canonical NFκB and activated non-canonical NFκB signaling. On the contrary, interfering of CD147 had no effect on NFκB signaling pathways as well as TRAF2 protein level in mouse spermatogonia cell line (GC-1 cells). Taken together, these results suggested that CD147 plays a key role in reducing extrinsic apoptosis in spermatocytes, but not spermatogonia, through modulating NFκB signaling pathway.