Fig. 2.

The schematic portrays crosstalk between miR29 family and various signal transduction pathways involved in pathogenesis of Diabetic Nephropathy. In mesangial cells, miR29a prevents activation of pro-fibrotic genes via targeting Wnt/β-Catenin signaling pathway and shows defensive role in renal fibrosis while in podocytes, in incidences of hyperglycaemia, downregulation of miR29a occurs which further rises HDAC4 expression ultimately resulting into podocytes’ inflammation followed by their impairment along with promotion of renal fibrosis via activation of TGF-β1 and Fibronectin. In contrast to this, miR29c causes activation of inflammatory cytokines and Rho-Kinase while suppression of TTP (anti-inflammatory protein) conferring to podocytes’ as well as proximal tubular cells’ inflammation. In proximal tubular cells, NF-κ β followed by Sirt1 causes downregulation of miR29 causing deregulation of Keap1/Nrf2 pathway subsequently causing RPTEC injury while renal fibrosis occurs due to three major factors i.e. TGF-β1, Ang II and DPP4 contributing to overexpression of ECM genes and downregulation of miR29a and miR29b. HDAC4, Histone deacetylase 4; TGF-β1, Transforming growth factor-β1; TTP, Tristetraprolin; NF-κβ, Nuclear factor-κβ; Keap1, Kelch-like ECH-associated protein 1; Nrf2, Nuclear factor erythroid 2; RPTEC, Renal proximal tubular epithelial cells; Ang II, Angiotensin II; DPP4, Dipeptidyl peptidase 4; ECM, Extracellular matrix