Extracellular Hmgb1 thus bound to TLR4, and by which, it activated MyD88-NFκB pathway to enhance IL-1β expression, which in turn promoted TGF-β/Smad2/3 and Pi3k/Akt signaling to exacerbate renal fibrosis. The gene discussed is TGFB1; the disease is renal fibrosis.