Targeting TGFβ to Treat Fibrotic Disease
TGFβ is an important component of the inflammatory signaling of senescent cells, and cellular senescence is involved in the progression of numerous fibrotic and age-related conditions. Chronic inflammation causes tissue maintenance processes to run awry, and fibrosis, the inappropriate deposition of scar-like collagen structures that disrupt tissue function, is one of the possible outcomes. Here, researchers use an established class of compound to target this form of inflammatory signaling, finding that the treatment has a positive impact on fibrotic disease in animal models. This is consistent with other studies that have found that TGFβ is a useful target, in that suppressing TGFβ signaling can limit the harms done by senescent cells.
Fibrotic disease is a major cause of mortality worldwide, with fibrosis arising from prolonged inflammation and aberrant extracellular matrix dynamics. Compromised cellular and tissue repair processes following injury, infection, metabolic dysfunction, autoimmune conditions, and vascular diseases leave tissues susceptible to unresolved inflammation, fibrogenesis, loss of function and scarring.
There has been limited clinical success with therapies for inflammatory and fibrotic diseases such that there remains a large unmet therapeutic need to restore normal tissue homoeostasis without detrimental side effects. We investigated the effects of a newly formulated low molecular weight dextran sulfate (LMW-DS), termed ILB, to resolve inflammation and activate matrix remodelling in rodent and human disease models. We demonstrated modulation of the expression of multiple pro-inflammatory cytokines and chemokines in vitro together with scar resolution and improved matrix remodelling in vivo.
Of particular relevance, we demonstrated that ILB acts, in part, by downregulating transforming growth factor (TGF)β signalling genes and by altering gene expression relating to extracellular matrix dynamics, leading to tissue remodelling, reduced fibrosis, and functional tissue regeneration. These observations indicate the potential of ILB to alleviate fibrotic diseases.
Elon Musk is asking on twitter what he should use his wealth on. Answer SRF.
heres the tweet
https://twitter.com/elonmusk/status/1347356316763705344?s=19
Too bad the compound can also have unacceptable side effects. Has anyone else researched
Pioglitazone as a TGF-B reducer?
https://pubmed.ncbi.nlm.nih.gov/16054559/
https://iovs.arvojournals.org/article.aspx?articleid=2516298
Besides the reduction benefits described in this post, reducing TGF-b should keep us looking a lot younger? Subcutaneous fat loss under skin ( loss of dermal fat) isa big reason we look old and bruise more easily. It seems that TGF-B is responsible for that.
https://www.the-dermatologist.com/news/transforming-growth-factor-beta-may-hold-key-age-related-loss-dermal-fat-immunity
https://www.fightaging.org/archives/2018/12/tgf-β-is-involved-in-the-loss-of-fat-and-bacterial-defenses-in-aging-skin/
https://www.labmedica.com/bioresearch/articles/294776448/blocking-expression-of-tgf-beta-preserves-healthy-skin.html
Is there anything better than low dose pio to take care of this ?
https://www.sciencedirect.com/science/article/pii/S0531556517305569
@august33
Boswellic Acid regulates NF-κB signaling, inhibits TNF-α (tumor necrosis factor-alpha) and TGF-β1.
Pirfenidone is an inhibitor for TGF-β production and TGF-β stimulated collagen production, reduces production of TNF-α and IL-1β, and also has anti-fibrotic and anti-inflammatory properties.
Thank you Jones! Why do some skin creams say they increase TGF-b in order to help with increasing collagen. Will inhibiting TFG-b make skin look older? It is very confusing as to whether you need more or less TGF-b, or if there is a trade off.
This article may shed some light about maintaining youthful dermal fat through inhibition of TGF-b by up regulating PPARy with low dose pioglitazone. Note however that it states " Future research will be needed to establish whether the TGF-β signaling blockade mediated by PPARγ is relevant to the maintenance of adipocyte state in human adipocytes."
https://www.nature.com/articles/s41598-020-71100-z
also this one. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5593428/
I saw this post when it was new and didn't fully understand the implications.
TGF beta along with IL-10 are hugely immune suppressive and upregulate all of the immune checkpoints causing age related immune dysfunction. If you can reduce IL-10 and TGF over time the elevated checkpoints has no stimulus keeping them on and they will reduce on their own.
You can measure IL-10 and TGF beta1 for less than $100 each with a doctor's order through Labcorp.
The active form of TGF beta is the one that actually matters but there isn't a practical way to measure it so you just have to live with the latent form measurement of TGFB1. There are papers showing the processing of the blood sample can give wide variations in the results almost to the point of meaninglessness so beware.
My own IL-10 and TGFB1 measured very high and I have less than ideal immune function and my facial and whole body fat has declined. I reduced my IL-10 with metoprolol and/or atovaquone. I will remeasure TGFB1 in a few weeks.
My pirfenidone is on order and in the meantime i'm doing a combination of pentoxifylline, metformin, valsartan/sacubatril and propanolol. My face got fatter in a good way in days but it is way too early to call this a win.
There is elevated cancer risk with pioglitazone so beware.