Autophagy: does it really help ? Is it a friend or a foe for peyronie's disease?

[Werther]

Hello everybody,

I'm writing this because I'm confused on this subject.

Does autophagy really help for peyronie's fibrosis?

I'm asking this because I've stumbled upon a series of papers which claim that autophagy, actually, represents the cause of several fibrotic disorders.

Unfortunately - as it could be imagined - I didn't come across papers talking specifically about peyronie's disease and autophagy.

Anyhow I've found some papers related to other fibrotic disorders where's claimed thath autophagy, instead of being beneficial, actually causes or aggravates the abovementioned illnesses.

Anyhow correct me if I misunderstood since English is not my motherlanguage.

Here is what I found:

"A systematic analysis of the LC3B-/- mice lungs revealed that aged LC3B-/- mice showed lung collagen deposition, increased cellularity, decreased alveolar spaces, increased apoptosis of AECII paralleled with surfactant alterations, increased lysosomal and endoplasmic reticulum stress providing clues on the importance of this distal autophagy protein in lung fibrosis development. Further, we were able to identify novel LC3B interaction partners within the AECII by mass spectrometric analysis which are being further confirmed. In conclusion, our studies reveal that autophagy has a pathomechanistic but context-specific role in the development of lung fibrosis (source: https://erj.ersjournals.com/content/50/suppl_61/OA478);

"we further study the inhibition of autophagy with siRNA Beclin 1 on HPMCs to confirm the contribution of autophagy in the HGPDS‐induced EMT, fibrosis and apoptosis. Our results demonstrate that autophagy inhibition reduced EMT, fibrosis and apoptosis in HPMCs" (source: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5783841/);

"Inhibition of key regulators of autophagy, LC3 and beclin-1, leads to the opposite effect on fibroblast expression of á-smooth muscle actin and fibronectin" (source: https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0041394);

"Accumulating evidence demonstrates that autophagy and selective autophagy exertpreviously unknown functions during thepathogenesis of human lung diseases. It isnow clear that autophagy plays a complexrole in the lung, where it can have bothprotective and injurious effects on theproccumulating evidence demonstrates thatautophagy and selective autophagy exertpreviously unknown functions during thepathogenesis of human lung diseases. It isnow clear that autophagy plays a complexrole in the lung, where it can have bothprotective and injurigression of lung disease" (source: https://www.atsjournals.org/doi/pdf/10.1513/AnnalsATS.201507-450MG).

I look foward to hear any feedback on this.

[pey ron]

similar to enalapril: found several papers saying it's a potent anti-fibrotic and then i found one paper saying it induces fibrosis

[NeoV]

Autophagy is a very general term that is applied to more than one thing. Autophagy is related to everything, including cancer.
Autophagy: Cancer's Friend or Foe?

The important question is rather, how does autophagy work with fasting and time restricted feeding? In which case, it is indeed therapeutic to fibrotic disorders and even cancer and other diseases.

[Werther]

I agree with what you said.

Problem is that, given that autophagy MIGHT be induced by calories' restriction, it's not clear if it might be helpful for fibrosis or not.

For instance, I've found another paper where's claimed that protein restriciton and intermittent fasting are good for preventing age-associated diseases but in the same article it's stated that :"Fibroblast growth factor 21 (FGF21) is implicated in the adaptive response to both starvation and KDs, and interventions that raise circulating FGF21 levels increase insulin sensitivity and energy expenditure. Laeger et al. showed that hepatic FGF21 expression is induced by dietary protein restriction (50% control). (source: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6036773/).

All of this is very confusing  

It looks like there's at least a chance that, besides getting no improvements, fasting could make things worse in the peyronie's department (unless I misunderstood something).