Abstract：Objective To investigate the effect and molecular mechanism of interferon-α (INF-α) on the apoptosis of the mouse podocyte cell line MPC5 induced by hepatitis B virus X (HBx) protein. Methods MPC5 cells were transfected with the pEX plasmid carrying the HBx gene. RT-PCR was used to measure the mRNA expression of HBx at different time points. MPC5 cells were divided into 4 groups:control group (MPC5 cells cultured under normal conditions), INF-α group (MPC5 cells cultured with INF-α), HBx group (MPC5 cells induced by HBx), and HBx+INF-α group (MPC5 cells induced by HBx and cultured with INF-α). After 48 hours of intervention under different experimental conditions, flow cytometry was used to measure the apoptosis of MPC5 cells, and quantitative real-time PCR and Western blot were used to measure the mRNA and protein expression of slit diaphragm-related proteins (nephrin, CD2AP, and synaptopodin) and the cytoskeleton-related protein transient receptor potential cation channel 6 (TRPC6). Results MPC5 cells transfected by pEX-HBx had the highest expression of HBx mRNA at 48 hours after transfection (P P P P Conclusions INF-α can inhibit the apoptosis of podocytes induced by HBx, possibly through improving the abnormal expression of slit diaphragm-related proteins (CD2AP, nephrin, and synaptopodin) and cytoskeleton-related protein (TRPC6) induced by HBx.
SUN Yong-Hong,LEI Xiao-Yan,CHEN Xing-Xing et al. Effect and molecular mechanism of interferon-α on podocyte apoptosis induced by hepatitis B virus X protein[J]. CJCP, 2019, 21(9): 930-935.
Mundel P, Reiser J. Proteinuria:an enzymatic disease of the podocyte[J]. Kidney Int, 2010, 77(7):571-580.
[2]
Clippinger AJ, Gearhart TL, Bouchard MJ. Hepatitis B virus X protein modulates apoptosis in primary rat hepatocytes by regulating both NF-kappaB and the mitochondrial permeability transition pore[J]. J Virol, 2009, 83(10):4718-4731.
Cai B, Cai JP, Luo YL, et al. The specific roles of JAK/STAT signaling pathway in sepsis[J]. Inflammation, 2015, 38(4):1599-1608.
[9]
Zhang Y, Chen Y, Yang F. HBx transfection limits proliferative capacity of podocytes through cell cycle regulation[J]. Acta Biochim Biophys Sin (Shanghai), 2014, 46(12):1016-1023.
Ma Y, Yang Q, Zhong Z, et al. Role of c-Abl and nephrin in podocyte cytoskeletal remodeling induced by angiotensin Ⅱ[J].Cell Death Dis, 2018, 9(2):185.
[12]
Kato T, Mizuno S, Kamimoto M. The decreases of nephrin and nuclear WTl in podoeytes may callse albuminuria during the experimental sepsis in mice[J]. Biomed Res, 2010, 31(6):363-369.
[13]
Lin SM, Lin CJ, Hsu CW, et al. Prospective randomized controlled study of interferon-alpha in preventing hepatocellular carcinoma recurrence after medical ablation therapy for primary tumors[J]. Cancer, 2004, 100(2):376-382.
[14]
Russo LM, Srivatsan S, Seaman M, et al. Albuminuria associated with CD2AP knockout mice is primarily due to dysfunction of the renal degradation pathway processing of filtered albumin[J]. FEBS Lett, 2013, 587(22):3738-3741.
[15]
Kim EY, Suh JM, Chiu YH, et al. Regulation of podocyte BK(Ca) channels by synaptopodin, Rho, and actin microfilaments[J]. Am J Physiol Renal Physiol, 2010, 299(3):F594-F604.
[16]
Zuo Y, Yang HC, Pothoff SA, et al. Protective effects of PPARγ agonist in acute nephrotic syndrome[J]. Nephrol Dial Transplant, 2012, 27(1):174-181.
[17]
Wilson C, Dryer SE. A mutation in TRPC6 channels abolishes their activation by hypoosmotic stretch but does not affect activation by diacylglycerol or G protein signaling cascades[J]. Am J Physiol Renal Physiol, 2014, 306(9):F1018-F1025.
