New insights into the pathogenesis of primary biliary cholangitis asymptomatic stage

Figure 1 Schematic of bicarbonate secretion by small and large cholangiocytes. AE2: Chloride/bicarbonate anion exchanger 2; TMEM16A: Transmembrane 16A chloride channels; ATP: Adenosine triphosphate; P2YR: Purinergic receptor family; InsP₃: Inositol-1,4,5-trisphosphate; InsP₃R3: Inositol-1,4,5-trisphosphate receptor type 3; ER: Endoplasmic reticulum; SR: Secretin receptor; cAMP: Cyclic adenosine monophosphate; Ach: Acetylcholine; CFTR: Cystic fibrosis transmembrane conductance regulator; M3R: Muscarinic acetylcholine M3 receptor; HCO₃^-: Bicarbonate; Cl^-: Chloride; Ca²⁺: Calcium.

Figure 2 Mechanism of inositol-1,4,5-trisphosphate receptor type 3 and chloride/carbonate (chloride/bicarbonate) anion exchanger 2 gene expression reduction due to the increase in the amount of micro-RNA 506 and its activity. InsP₃R3: Inositol-1,4,5-trisphosphate receptor type 3; AE2: Chloride/bicarbonate anion exchanger 2; miR-506: Micro-RNA 506; TMEM16A: Transmembrane 16A chloride channels; HCO₃^-: Bicarbonate; Cl^-: Chloride.

Figure 3 Solubilization of phospholipids and cholesterol from membrane structures by bile acids. BA: Bile acids.

Figure 4 Mechanism of anti-mitochondrial antibody formation, development of ductulopenia, weakness, fatigue and malaise in the asymptomatic stage of primary biliary cholangitis: hypothesis. InsP₃R3: Inositol-1,4,5-trisphosphate receptor type 3; AE2: Chloride/bicarbonate anion exchanger 2; PDG: Pyruvate dehydrogenase; ATP: Adenosine triphosphate.