Background Chronic kidney disease (CKD) is characterized by high morbidity and mortality and is difficult to cure. Renal interstitial fibrosis (RIF) is a major determinant of, and commonly occurs within, CKD progression. Epithelial mesenchymal transition (EMT) has been identified as a crucial process in triggering renal interstitial fibrosis (RIF). Interleukin‐like EMT inducer (ILEI) is an important promotor of EMT; this study aims to elucidate the mechanisms involved. Methods Male C57BL6/J mouse were randomly divided into 6 groups: sham (n = 10), sham with negative control (NC) shRNA (sham + NC, n = 10), sham with ILEI shRNA (sham + shILEI, n = 10), unilateral ureteral obstruction (UUO, n = 10), UUO with NC (UUO + NC, n = 10) and UUO with ILEI shRNA (UUO + shILEI, n = 10). Hematoxylin and eosin (H&E), Masson, and immunohistochemical (IHC) staining and western blotting (WB) were performed on murine kidney tissue to identify the function and mechanism of ILEI in RIF. In vitro, ILEI was overexpressed to induce EMT in HK2 cells and analyzed via transwell, WB, real-time PCR, and co-immunoprecipitation. Finally, tissue from 12 pediatric CKD patients (seven with RIF and five without RIF) were studied with H&E, Masson, and IHC staining. Results Our in vitro model revealed that ILEI facilitates RIF in the UUO model via the Akt and ERK pathways. Further experiments in vivo and in vitro revealed that ILEI promotes renal tubular EMT by binding and activating leukemia inhibitory factor receptor (LIFR), in which phosphorylation of Akt and ERK is involved. We further find markedly increased expression levels of ILEI and LIFR in kidneys from pediatric CKD patients with RIF. Conclusion Our results indicate that ILEI may be a useful biomarker for renal fibrosis and a potential therapeutic target for modulating RIF.

Objectives T peripheral helper (Tph) cells have major roles in pathological processes in systemic lupus erythematosus (SLE). We sought to clarify the mechanisms of Tph cell differentiation and their relevance to clinical features in patients with SLE. Method Phenotypes and functions of Tph cell–related markers in human CD4+ T cells purified from volunteers or patients were analyzed using flow cytometry and quantitative PCR. Renal biopsy specimens from patients with lupus nephritis (LN) were probed by multicolor immunofluorescence staining. Results Among multiple cytokines, transforming growth factor (TGF)-β3 characteristically induced programmed cell death protein 1 (PD-1) hi musculoaponeurotic fibrosarcoma (MAF)+, interleukin (IL)-21+IL-10+ Tph-like cells with a marked upregulation of related genes including PDCD-1, MAF, SOX4, and CXCL13. The induction of Tph-like cells by TGF-β3 was suppressed by the neutralization of TGF-β type II receptor (TGF-βR2). TGF-β3-induced Tph-like cells efficiently promoted the differentiation of class-switch memory B cells into plasmocytes, resulting in enhanced antibody production. The proportion of Tph cells in the peripheral blood was significantly increased in patients with SLE than in healthy volunteers in concordance with disease activity and severity of organ manifestations such as LN. TGF-β3 was strongly expressed on macrophages, which was associated with the accumulation of CD4+ C-X-C chemokine receptor (CXCR5)-PD-1+ Tph cells, in the renal tissue of patients with active LN. Conclusion The induction of Tph-like cells by TGF-β3 mainly produced from tissue macrophages plays a pivotal role in the pathological processes of active LN by enhancing B cell differentiation in patients with SLE.

Background: Renal interstitial fibrosis is accepted as a crucial component of chronic kidney diseases (CKD). Epithelial-mesenchymal transition (EMT) is an important factor contributing to renal interstitial fibrosis.Livin, due to its ability to induce EMT, is an important regulator of many types of tumors and might also be involved in human renal tubular EMT.Methods: We confirmed that Livin and lncRNA-ATB could aggravate EMT in vivo and in vitro, lncRNA-ATB could be suppressed by the silencing of Livin whereas Livin expression was nearly stable when lncRNA-ATB was overexpressed or knocked out.Results: Livin was upregulated in vivo and in vitro at the similar rate as the occurrence of EMT, which could be relieved when Livin was silenced. LncRNA-ATB, which is another important regulator of EMT, was also found highly expressed during this process. The silencing of lncRNA-ATB could lessen the severity of EMT, and the overexpression of lncRNA-ATB could aggravate EMT without affecting the expression of Livin.Conclusions: Livin promotes EMT through the regulation of lncRNA-ATB. The silencing of Livin might be an effective targeted therapy for renal fibrosis.