Thymosin β4 up-regulation of microRNA-146a promotes oligodendrocyte differentiation and suppression of the Toll-like proinflammatory pathway.

Santra M, Zhang ZG, Yang J, Santra S, Santra S, Chopp M, Morris DC

The Journal of biological chemistry14 May 2014Cited by 57 (Europe PMC)

PMID24828499PMCIDPMC4094061DOI10.1074/jbc.m113.529966PepBankPUB-24828499

Summary

Thymosin β4 (Tβ4), a G-actin-sequestering peptide, improves neurological outcome in rat models of neurological injury. Tissue inflammation results from neurological injury, and regulation of the inflammatory response is vital for neurological recovery. The innate immune response system, which includes the Toll-like receptor (TLR) proinflammatory signaling pathway, regulates tissue injury. We hypothesized that Tβ4 regulates the TLR proinflammatory signaling pathway. Because oligodendrogenesis plays an important role in neurological recovery, we employed an in vitro primary rat embryonic cell model of oligodendrocyte progenitor cells (OPCs) and a mouse N20.1 OPC cell line to measure the effects of Tβ4 on the TLR pathway. Cells were grown in the presence of Tβ4, ranging from 25 to 100 ng/ml (RegeneRx Biopharmaceuticals Inc., Rockville, MD), for 4 days. Quantitative real-time PCR data demonstrated that Tβ4 treatment increased expression of microRNA-146a (miR-146a), a negative regulator the TLR signaling pathway, in these two cell models. Western blot analysis showed that Tβ4 treatment suppressed expression of IL-1 receptor-associated kinase 1 (IRAK1) and tumor necrosis factor receptor-associated factor 6 (TRAF6), two proinflammatory cytokines of the TLR signaling pathway. Transfection of miR-146a into both primary rat embryonic OPCs and mouse N20.1 OPCs treated with Tβ4 demonstrated an amplification of myelin basic protein (MBP) expression and differentiation of OPC into mature MBP-expressing oligodendrocytes. Transfection of anti-miR-146a nucleotides reversed the inhibitory effect of Tβ4 on IRAK1 and TRAF6 and decreased expression of MBP. These data suggest that Tβ4 suppresses the TLR proinflammatory pathway by up-regulating miR-146a.

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

Results from this study7

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

01LabIn vitro (cells)Mechanism
In primary rat and mouse N20.1 oligodendrocyte progenitor cells, Tβ4 treatment increased microRNA-146a expression.
In plain wordsIn cells, Tβ4 increased the level of microRNA-146a, a brake on a pro-inflammatory pathway.
Peptide
Thymosin beta-4 (human)
Outcome
IncreasemiR-146a expression
Study
rat and mousen: not reported in source
primary rat embryonic OPCs and mouse N20.1 OPC cell line
Outcome group
Inflammation markers · Nervous system and cognition
Studied dose
25-100 ng/ml · 4 daysAs given in this study (rat and mouse).
Source sentences
Summary
Quantitative real-time PCR data demonstrated that Tβ4 treatment increased expression of microRNA-146a (miR-146a), a negative regulator the TLR signaling pathway, in these two cell models.
2 context sentences(design, population, supporting numbers)
Summary · context
Because oligodendrogenesis plays an important role in neurological recovery, we employed an in vitro primary rat embryonic cell model of oligodendrocyte progenitor cells (OPCs) and a mouse N20.1 OPC cell line to measure the effects of Tβ4 on the TLR pathway.
Summary · context
Cells were grown in the presence of Tβ4, ranging from 25 to 100 ng/ml (RegeneRx Biopharmaceuticals Inc., Rockville, MD), for 4 days.
Show in the study text Report a problemFND-2482849901
02LabIn vitro (cells)Mechanism
In oligodendrocyte progenitor cells, Tβ4 treatment suppressed expression of IRAK1 in the TLR pathway.
In plain wordsIn cells, Tβ4 lowered IRAK1, a protein of a pro-inflammatory pathway.
Peptide
Thymosin beta-4 (human)
Outcome
DecreaseIRAK1 expression
Study
rat and mousen: not reported in source
primary rat embryonic OPCs and mouse N20.1 OPC cell line
Outcome group
Inflammation markers · Nervous system and cognition
Studied dose
25-100 ng/ml · 4 daysAs given in this study (rat and mouse).
Source sentences
Summary
Western blot analysis showed that Tβ4 treatment suppressed expression of IL-1 receptor-associated kinase 1 (IRAK1) and tumor necrosis factor receptor-associated factor 6 (TRAF6), two proinflammatory cytokines of the TLR signaling pathway.
2 context sentences(design, population, supporting numbers)
Summary · context
Because oligodendrogenesis plays an important role in neurological recovery, we employed an in vitro primary rat embryonic cell model of oligodendrocyte progenitor cells (OPCs) and a mouse N20.1 OPC cell line to measure the effects of Tβ4 on the TLR pathway.
Summary · context
Cells were grown in the presence of Tβ4, ranging from 25 to 100 ng/ml (RegeneRx Biopharmaceuticals Inc., Rockville, MD), for 4 days.
Show in the study text Report a problemFND-2482849902
03LabIn vitro (cells)Mechanism
In oligodendrocyte progenitor cells, Tβ4 treatment suppressed expression of TRAF6 in the TLR pathway.
In plain wordsIn cells, Tβ4 lowered TRAF6, a protein of a pro-inflammatory pathway.
Peptide
Thymosin beta-4 (human)
Outcome
DecreaseTRAF6 expression
Study
rat and mousen: not reported in source
primary rat embryonic OPCs and mouse N20.1 OPC cell line
Outcome group
Inflammation markers · Nervous system and cognition
Studied dose
25-100 ng/ml · 4 daysAs given in this study (rat and mouse).
Source sentences
Summary
Western blot analysis showed that Tβ4 treatment suppressed expression of IL-1 receptor-associated kinase 1 (IRAK1) and tumor necrosis factor receptor-associated factor 6 (TRAF6), two proinflammatory cytokines of the TLR signaling pathway.
2 context sentences(design, population, supporting numbers)
Summary · context
Because oligodendrogenesis plays an important role in neurological recovery, we employed an in vitro primary rat embryonic cell model of oligodendrocyte progenitor cells (OPCs) and a mouse N20.1 OPC cell line to measure the effects of Tβ4 on the TLR pathway.
Summary · context
Cells were grown in the presence of Tβ4, ranging from 25 to 100 ng/ml (RegeneRx Biopharmaceuticals Inc., Rockville, MD), for 4 days.
Show in the study text Report a problemFND-2482849903

Studies that did not test the peptide alone4

In this study, Thymosin beta-4 (human) was a lab tool or a carrier, part of a mix, or the subject of a lab method. These results are not evidence about taking Thymosin beta-4 (human).

04LabNot a test of Thymosin beta-4 (human) aloneIn vitro (cells)Mechanism
In Tβ4-treated oligodendrocyte progenitor cells, transfection of miR-146a amplified myelin basic protein expression.
In plain wordsIn cells treated with Tβ4, adding extra miR-146a increased the amount of myelin basic protein.
Peptide
Thymosin beta-4 (human)
Outcome
IncreaseMBP expression with miR-146a transfection in Tβ4-treated cells
Study
rat and mousen: not reported in source
primary rat embryonic OPCs and mouse N20.1 OPC cell line
Outcome group
Neuroprotection · Nervous system and cognition
Source sentences
Summary
Transfection of miR-146a into both primary rat embryonic OPCs and mouse N20.1 OPCs treated with Tβ4 demonstrated an amplification of myelin basic protein (MBP) expression and differentiation of OPC into mature MBP-expressing oligodendrocytes.
2 context sentences(design, population, supporting numbers)
Summary · context
Because oligodendrogenesis plays an important role in neurological recovery, we employed an in vitro primary rat embryonic cell model of oligodendrocyte progenitor cells (OPCs) and a mouse N20.1 OPC cell line to measure the effects of Tβ4 on the TLR pathway.
Summary · context
Cells were grown in the presence of Tβ4, ranging from 25 to 100 ng/ml (RegeneRx Biopharmaceuticals Inc., Rockville, MD), for 4 days.
In this study, Thymosin beta-4 (human) was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking Thymosin beta-4 (human).
Show in the study text Report a problemFND-2482849904
05LabNot a test of Thymosin beta-4 (human) aloneIn vitro (cells)Mechanism
In Tβ4-treated oligodendrocyte progenitor cells, transfection of miR-146a amplified differentiation into mature MBP-expressing oligodendrocytes.
In plain wordsIn cells treated with Tβ4, adding extra miR-146a increased the change into mature myelin-making cells.
Peptide
Thymosin beta-4 (human)
Outcome
IncreaseDifferentiation into MBP-expressing oligodendrocytes with miR-146a transfection in Tβ4-treated cells
Study
rat and mousen: not reported in source
primary rat embryonic OPCs and mouse N20.1 OPC cell line
Outcome group
Neuroprotection · Nervous system and cognition
Source sentences
Summary
Transfection of miR-146a into both primary rat embryonic OPCs and mouse N20.1 OPCs treated with Tβ4 demonstrated an amplification of myelin basic protein (MBP) expression and differentiation of OPC into mature MBP-expressing oligodendrocytes.
2 context sentences(design, population, supporting numbers)
Summary · context
Because oligodendrogenesis plays an important role in neurological recovery, we employed an in vitro primary rat embryonic cell model of oligodendrocyte progenitor cells (OPCs) and a mouse N20.1 OPC cell line to measure the effects of Tβ4 on the TLR pathway.
Summary · context
Cells were grown in the presence of Tβ4, ranging from 25 to 100 ng/ml (RegeneRx Biopharmaceuticals Inc., Rockville, MD), for 4 days.
In this study, Thymosin beta-4 (human) was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking Thymosin beta-4 (human).
Show in the study text Report a problemFND-2482849905
06LabNot a test of Thymosin beta-4 (human) aloneIn vitro (cells)Mechanism
In Tβ4-treated oligodendrocyte progenitor cells, anti-miR-146a reversed the inhibitory effect of Tβ4 on IRAK1 and TRAF6.
In plain wordsIn cells, blocking miR-146a removed the lowering effect of Tβ4 on IRAK1 and TRAF6.
Peptide
Thymosin beta-4 (human)
Outcome
IncreaseIRAK1 and TRAF6 expression with anti-miR-146a
Study
rat and mousen: not reported in source
primary rat embryonic OPCs and mouse N20.1 OPC cell line
Outcome group
Inflammation markers · Nervous system and cognition
Source sentences
Summary
Transfection of anti-miR-146a nucleotides reversed the inhibitory effect of Tβ4 on IRAK1 and TRAF6 and decreased expression of MBP.
2 context sentences(design, population, supporting numbers)
Summary · context
Because oligodendrogenesis plays an important role in neurological recovery, we employed an in vitro primary rat embryonic cell model of oligodendrocyte progenitor cells (OPCs) and a mouse N20.1 OPC cell line to measure the effects of Tβ4 on the TLR pathway.
Summary · context
Cells were grown in the presence of Tβ4, ranging from 25 to 100 ng/ml (RegeneRx Biopharmaceuticals Inc., Rockville, MD), for 4 days.
In this study, Thymosin beta-4 (human) was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking Thymosin beta-4 (human).
Show in the study text Report a problemFND-2482849906
07LabNot a test of Thymosin beta-4 (human) aloneIn vitro (cells)Mechanism
In Tβ4-treated oligodendrocyte progenitor cells, anti-miR-146a decreased myelin basic protein expression.
In plain wordsIn cells, blocking miR-146a lowered the amount of myelin basic protein.
Peptide
Thymosin beta-4 (human)
Outcome
DecreaseMBP expression with anti-miR-146a
Study
rat and mousen: not reported in source
primary rat embryonic OPCs and mouse N20.1 OPC cell line
Outcome group
Neuroprotection · Nervous system and cognition
Source sentences
Summary
Transfection of anti-miR-146a nucleotides reversed the inhibitory effect of Tβ4 on IRAK1 and TRAF6 and decreased expression of MBP.
2 context sentences(design, population, supporting numbers)
Summary · context
Because oligodendrogenesis plays an important role in neurological recovery, we employed an in vitro primary rat embryonic cell model of oligodendrocyte progenitor cells (OPCs) and a mouse N20.1 OPC cell line to measure the effects of Tβ4 on the TLR pathway.
Summary · context
Cells were grown in the presence of Tβ4, ranging from 25 to 100 ng/ml (RegeneRx Biopharmaceuticals Inc., Rockville, MD), for 4 days.
In this study, Thymosin beta-4 (human) was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking Thymosin beta-4 (human).
Show in the study text Report a problemFND-2482849907

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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