Transforming Growth Factor-β and Long Non-coding RNA in Renal Inflammation and Fibrosis

Abstract

Renal fibrosis is one of the most characterized pathological features in chronic kidney disease (CKD). Progressive fibrosis eventually leads to renal failure, leaving dialysis or allograft transplantation the only clinical option for CKD patients. Transforming growth factor-β (TGF-β) is the key mediator in renal fibrosis and is an essential regulator for renal inflammation. Therefore, the general blockade of the pro-fibrotic TGF-β may reduce fibrosis but may risk promoting renal inflammation and other side effects due to the diverse role of TGF-β in kidney diseases. Long non-coding RNAs (lncRNAs) are RNA transcripts with more than 200 nucleotides and have been regarded as promising therapeutic targets for many diseases. This review focuses on the importance of TGF-β and lncRNAs in renal inflammation, fibrogenesis, and the potential applications of TGF-β and lncRNAs as the therapeutic targets and biomarkers in renal fibrosis and CKD are highlighted.

Keywords: SMADs; TGF-β; inflammation; long non-coding RNA; molecular therapy; renal fibrosis.

FIGURE 1

Renal intrinsic and inflammatory cells in glomerular and interstitial fibrosis during kidney injury. Damaged mesangial cells (MCs), endothelial cells (ECs), and podocytes are essential in the glomerular fibrosis. The mesangial cell may produce pro-fibrotic and pro-inflammatory growth factors and cytokines and enhance proliferation to cause deposition of the mesangial matrix. Damages on endothelial cells and podocytes may lead to albuminuria and endothelial dysfunction in chronic kidney disease (CKD). Injured tubular epithelial cells (TECs) may produce pro-fibrotic and pro-inflammatory factors, resulting in the accumulation of extracellular matrix (ECM) and inflammatory cells in the tubulointerstitium area. Immune cells, including macrophages and T cells, may participate in renal fibrosis by producing growth factors and becoming collagen-producing myofibroblasts under the regulation of transforming growth factor-β (TGF-β)/Smad3 signaling.