Recombinant human Thymosin β4 ameliorates experimental colitis and intestinal fibrosis through suppression of mineralocorticoid receptor signaling.

Zhao TR, Hu EB, Wang MW, Zhai YF, Mao YY, Hou WY, Zhang XZ, Liu ZZ, Hou SL, Xu JJ, Yu R

Molecular biomedicine17 Aug 2026

PMID42606759PMCIDPMC13481925DOI10.1186/s43556-026-00539-9PepBankPUB-42606759

Summary

Inflammatory bowel disease (IBD) is a chronic inflammatory disorder characterized by epithelial barrier disruption, persistent mucosal inflammation, and progressive intestinal fibrosis, for which effective therapeutic options remain limited. Thymosin β4 (Tβ4) is a highly conserved endogenous peptide with established roles in tissue repair and immune regulation, but its contribution to IBD pathogenesis has not been fully elucidated. Here, we found that TMSB4X, the gene encoding Tβ4, was downregulated in colonic tissues of IBD patients. To investigate its functional significance, we generated Tmsb4x-deficient mice and demonstrated that loss of endogenous Tβ4 markedly increased susceptibility to dextran sulfate sodium (DSS)-induced colitis. Conversely, oral administration of recombinant human Tβ4 (rhTβ4) significantly improved survival, alleviated body weight loss, reduced epithelial injury, and suppressed inflammatory cytokine production in both prophylactic and therapeutic colitis models. Furthermore, rhTβ4 attenuated intestinal fibrosis, as evidenced by reduced expression of fibrosis-associated markers and decreased collagen I deposition. Transcriptomic analysis revealed that rhTβ4 partially restored DSS-induced gene dysregulation and suppressed mineralocorticoid receptor (MR, NR3C2) signaling, a pathway further supported by reporter assays and downstream target gene analyses. Collectively, these findings identify Tβ4 as an endogenous protective factor against intestinal inflammation and fibrosis and suggest that pharmacological restoration of Tβ4 activity may represent a promising therapeutic strategy for IBD through modulation of mineralocorticoid receptor signaling.

CC BYText from Europe PMC. Highlighted sentences are the source of results.

Results from this study10

8 results from studies that gave the peptide. No result from this study comes from people.

01AnimalAnimal study (in vivo)Efficacy outcome
In mice with DSS-induced colitis, oral recombinant human Tβ4 significantly improved survival in prophylactic and therapeutic models.
In plain wordsIn mice with colitis, oral Tβ4 improved survival.
Peptide
Thymosin beta-4 (human)
Outcome
IncreaseSurvival in DSS colitis
Study
mousen: not reported in source
DSS-induced colitis
Outcome group
Mortality · Gastrointestinal
Studied dose
Dose not stated · oralAs given in this study (mouse).
Source sentences
Summary
oral administration of recombinant human Tβ4 (rhTβ4) significantly improved survival
Show in the study text Report a problemFND-4260675903
02AnimalAnimal study (in vivo)Efficacy outcome
In mice with DSS-induced colitis, oral recombinant human Tβ4 alleviated body weight loss.
In plain wordsIn mice with colitis, oral Tβ4 reduced weight loss.
Peptide
Thymosin beta-4 (human)
Outcome
DecreaseBody weight loss in DSS colitis
Study
mousen: not reported in source
DSS-induced colitis
Outcome group
Body weight · Gastrointestinal
Studied dose
Dose not stated · oralAs given in this study (mouse).
Source sentences
Summary
alleviated body weight loss
1 context sentence(design, population, supporting numbers)
Summary · context
oral administration of recombinant human Tβ4 (rhTβ4)
Show in the study text Report a problemFND-4260675904
03AnimalAnimal study (in vivo)Efficacy outcome
In mice with DSS-induced colitis, oral recombinant human Tβ4 reduced epithelial injury.
In plain wordsIn mice with colitis, oral Tβ4 reduced damage to the gut lining.
Peptide
Thymosin beta-4 (human)
Outcome
DecreaseEpithelial injury in DSS colitis
Study
mousen: not reported in source
DSS-induced colitis
Outcome group
Gastrointestinal protection · Gastrointestinal
Studied dose
Dose not stated · oralAs given in this study (mouse).
Source sentences
Summary
reduced epithelial injury
1 context sentence(design, population, supporting numbers)
Summary · context
oral administration of recombinant human Tβ4 (rhTβ4)
Show in the study text Report a problemFND-4260675905
04AnimalAnimal study (in vivo)Efficacy outcome
In mice with DSS-induced colitis, oral recombinant human Tβ4 suppressed inflammatory cytokine production.
In plain wordsIn mice with colitis, oral Tβ4 lowered inflammatory signals.
Peptide
Thymosin beta-4 (human)
Outcome
DecreaseInflammatory cytokine production in DSS colitis
Study
mousen: not reported in source
DSS-induced colitis
Outcome group
Inflammation markers · Gastrointestinal
Studied dose
Dose not stated · oralAs given in this study (mouse).
Source sentences
Summary
suppressed inflammatory cytokine production in both prophylactic and therapeutic colitis models
1 context sentence(design, population, supporting numbers)
Summary · context
oral administration of recombinant human Tβ4 (rhTβ4)
Show in the study text Report a problemFND-4260675906
05AnimalAnimal study (in vivo)Efficacy outcome
In mice with colitis, recombinant human Tβ4 attenuated intestinal fibrosis, with reduced expression of fibrosis-associated markers.
In plain wordsIn mice with colitis, Tβ4 reduced scarring-related markers in the gut.
Peptide
Thymosin beta-4 (human)
Outcome
DecreaseFibrosis-associated marker expression
Study
mousen: not reported in source
DSS-induced colitis
Outcome group
Gastrointestinal protection · Gastrointestinal
Studied dose
Dose not stated · oralAs given in this study (mouse).
Source sentences
Summary
rhTβ4 attenuated intestinal fibrosis, as evidenced by reduced expression of fibrosis-associated markers
Show in the study text Report a problemFND-4260675907
06AnimalAnimal study (in vivo)Efficacy outcome
In mice with colitis, recombinant human Tβ4 decreased collagen I deposition.
In plain wordsIn mice with colitis, Tβ4 reduced collagen build-up in the gut.
Peptide
Thymosin beta-4 (human)
Outcome
DecreaseCollagen I deposition
Study
mousen: not reported in source
DSS-induced colitis
Outcome group
Gastrointestinal protection · Gastrointestinal
Studied dose
Dose not stated · oralAs given in this study (mouse).
Source sentences
Summary
decreased collagen I deposition
Show in the study text Report a problemFND-4260675908
07AnimalAnimal study (in vivo)Mechanism
In transcriptomic analysis of mice with colitis, recombinant human Tβ4 partially restored DSS-induced gene dysregulation.
In plain wordsIn mice with colitis, Tβ4 partly restored gene activity that the chemical trigger had disturbed.
Peptide
Thymosin beta-4 (human)
Outcome
Not applicableDSS-induced gene dysregulation
Study
mousen: not reported in source
DSS-induced colitis
Outcome group
Receptor activity and mechanism · Gastrointestinal
Studied dose
Dose not stated · oralAs given in this study (mouse).
Source sentences
Summary
rhTβ4 partially restored DSS-induced gene dysregulation
Show in the study text Report a problemFND-4260675909
08AnimalAnimal study (in vivo)Mechanism
In mice with colitis, recombinant human Tβ4 suppressed mineralocorticoid receptor signaling, supported by reporter assays and downstream target gene analyses.
In plain wordsIn mice with colitis, Tβ4 reduced signaling through the mineralocorticoid receptor.
Peptide
Thymosin beta-4 (human)
Outcome
DecreaseMineralocorticoid receptor (NR3C2) signaling
Study
mousen: not reported in source
DSS-induced colitis
Outcome group
Receptor activity and mechanism · Gastrointestinal
Studied dose
Dose not stated · oralAs given in this study (mouse).
Source sentences
Summary
suppressed mineralocorticoid receptor (MR, NR3C2) signaling, a pathway further supported by reporter assays and downstream target gene analyses
Show in the study text Report a problemFND-4260675910

Natural levels measured2

These results measure the body's own peptide. Nobody was given the peptide. They are not evidence about taking it. They are left out of key results, evidence counts and charts.

09HumanEndogenous levelObservational studyOther
In colonic tissue of patients with inflammatory bowel disease, expression of TMSB4X, the gene encoding Tβ4, was downregulated.
In plain wordsIn patients with inflammatory bowel disease, the gene for the body's own Tβ4 was less active in colon tissue.
Peptide
Thymosin beta-4 (human)
Outcome
DecreaseTMSB4X expression in colonic tissue of IBD patients
Study
n: not reported in source
Outcome group
Inflammation markers · Gastrointestinal
Source sentences
Summary
Here, we found that TMSB4X, the gene encoding Tβ4, was downregulated in colonic tissues of IBD patients.
This result measures the body's own Thymosin beta-4 (human). Nobody was given the peptide. It is not evidence about taking it.
Show in the study text Report a problemFND-4260675901
10AnimalEndogenous levelAnimal study (in vivo)Mechanism
In mice, loss of endogenous Tβ4 markedly increased susceptibility to dextran sulfate sodium-induced colitis.
In plain wordsIn mice, lacking the body's own Tβ4 made colitis from a chemical trigger more likely.
Peptide
Thymosin beta-4 (human)
Outcome
IncreaseSusceptibility to DSS-induced colitis in Tmsb4x-deficient mice
Study
mousen: not reported in source
Tmsb4x-deficient mice, DSS colitis
Outcome group
Gastrointestinal protection · Gastrointestinal
Source sentences
Summary
we generated Tmsb4x-deficient mice and demonstrated that loss of endogenous Tβ4 markedly increased susceptibility to dextran sulfate sodium (DSS)-induced colitis
This result measures the body's own Thymosin beta-4 (human). Nobody was given the peptide. It is not evidence about taking it.
Show in the study text Report a problemFND-4260675902

AI wrote and checked these results. AI can make mistakes, so check important results against the source.

Version history

PepBank keeps every version of the data on this study. Status changes from Retraction Watch, Europe PMC and Crossref are listed with their source.

Version 2Current
13 Oct 2026, 01:52 UTC
Study results updated
Version 1
12 Oct 2026, 18:17 UTC
First added · source update from Europe PMC

Subjects

Terms as the source lists them.

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