PMID- 34642260 OWN - NLM STAT- MEDLINE DCOM- 20220113 LR - 20220531 IS - 1899-1505 (Electronic) IS - 0867-5910 (Linking) VI - 72 IP - 2 DP - 2021 Apr TI - The factors involved in the induction of neutrophil gelatinase-associated lipocalin overexpression in renal tubular epithelial cells under endoplasmic reticulum stress. LID - 10.26402/jpp.2021.2.14 [doi] AB - Our previous work found that neutrophil gelatinase-associated lipocalin (NGAL) expression increases when endoplasmic reticulum stress (ERS) occurs in human kidney-2 (HK-2) tubular epithelial cells. However, the reason for this is not yet known. This study investigated the factors involved when inducing NGAL overexpression in HK-2 cells during ERS. The cells were divided into six groups: the control group (normal HK-2 cells), the ERS group (HK-2 cells cultured in complete medium with thapsigargin (TG)), the transfection group (HK-2 cells transfected with activating transcription factor 4 small interfering ribonucleic acid (ATF4 siRNA), the ERS after transfection group (HK-2 cells transfected with ATF4 siRNA, then cultured in complete medium with TG), the negative control group (HK-2 cells transfected with siRNA-negative contrast), and the dimethyl sulfoxide (DMSO) group (HK-2 cells cultured in complete medium with DMSO). Western blot and a real-time polymerase chain reaction were used to measure the expression of protein and messenger ribonucleic acid (mRNA). As a result NGAL, ATF4, C/EBP homologous protein, glucose-regulated protein 78 kDa, ATF4 mRNA, and NGAL mRNA were clearly overexpressed in the ERS group compared with the control group (p < 0.05). The expression of NGAL and ATF4 were similar in the control group, the negative control group, and the DMSO group (p > 0.05). Meanwhile, ATF4, NGAL, ATF4 mRNA, and NGAL mRNA in the ERS after transfection group were significantly lower compared with the ERS group (p < 0.05), which showed that NGAL was affected by ATF4. There was a close correlation between NGAL and ATF4; when the expression of ATF4 was inhibited, NGAL was significantly lower. Therefore, ATF4 may be one of the upstream regulators of NGAL. FAU - Fu, T AU - Fu T AD - Department of Pediatrics, Shengjing Hospital of China Medical University, Shenyang, China. FAU - Hou, L AU - Hou L AD - Department of Pediatrics, Shengjing Hospital of China Medical University, Shenyang, China. FAU - Du, Y AU - Du Y AD - Department of Pediatrics, Shengjing Hospital of China Medical University, Shenyang, China. drduyue24@163.com. LA - eng PT - Journal Article DEP - 20210710 PL - Poland TA - J Physiol Pharmacol JT - Journal of physiology and pharmacology : an official journal of the Polish Physiological Society JID - 9114501 RN - 0 (Lipocalin-2) RN - 0 (RNA, Messenger) SB - IM MH - *Endoplasmic Reticulum Stress MH - *Epithelial Cells MH - Humans MH - Lipocalin-2/genetics MH - RNA, Messenger MH - Transfection EDAT- 2021/10/14 06:00 MHDA- 2022/01/14 06:00 CRDT- 2021/10/13 06:21 PHST- 2021/03/14 00:00 [received] PHST- 2021/04/30 00:00 [accepted] PHST- 2021/10/13 06:21 [entrez] PHST- 2021/10/14 06:00 [pubmed] PHST- 2022/01/14 06:00 [medline] AID - 10.26402/jpp.2021.2.14 [doi] PST - ppublish SO - J Physiol Pharmacol. 2021 Apr;72(2). doi: 10.26402/jpp.2021.2.14. Epub 2021 Jul 10.