Autophagy May Precede Cellular Senescence of Bile Ductular Cells in Ductular Reaction in Primary Biliary Cirrhosis

Abstract

Background and Aim. Recent studies disclosed that autophagy facilitates the process of

Primary Biliary Cirrhosis: Bad Genes, Bad Luck

“…In the current issue of Digestive Diseases and Sciences, Sasaki and colleagues [27] not only confirm their previous findings that autophagy is strongly linked to BEC senescence in PBC [24], but clearly demonstrate that autophagy precede cellular senescence of BEC. The major strength of this study is the staining of this large collection of liver tissues from patients with PBC and controls.…”

Autophagy Induces Prosenescent Changes in Proximal Tubular S3 Segments

“…[9][10][11][12] In summary, the observation that autophagy facilitates the establishment of a senescence phenotype and prevents clearance of potentially harmful cells is crucial in light of potential novel therapies to treat AKI by unselective enhancement of autophagy. 7 Additional research should focus on strategies for modulating autophagy that can be adapted for varied conditions and individual cellular stress levels.…”

“…8 Importantly, activation of both processes might be functionally linked: autophagy can facilitate senescence induction under various circumstances and in various cell types. [9][10][11] The underlying molecular mechanism explaining this prosenescent nature might be the need of autophagic degradation of an inhibitory isoform of p53 to suppress replicative senescence. 12 To test the potential interdependence of autophagy and cellular senescence, autophagy-related 5 (Atg5) protein was deleted in tubular epithelial cells.…”

Is Cellular Senescence Involved in Progressive Loss of Canals of Hering in Primary Biliary Cirrhosis?

“…While the exact mechanism(s) for progressive CoH loss remains speculative, there are several interesting hypotheses: i) CoH or bile ductules being destroyed by an immune attack [6] or ii) cellular senescence leading to impaired replacement and eventual loss of bile ductules and CoH [9,10].…”

“…Recent studies showed that cellular senescence was implicated in several biliary diseases and also premature or stress-induced senescence was discussed with respect to senescence-associated secretory phenotype (SASP) which is associated with microenvironments of affected cells or tissues [11,12]. Interestingly, Sasaki et al reported that bile ductules showed cellular senescence in PBC, and that sustained cellular senescence might lead to the eventual loss of bile ductules and CoH loss [9,10]. It is, moreover, reported that senescence is propagated through positive feedback by nearby senescent cells, causing senescence of adjacent bile ductules and CoH in PBC [11,12].…”