High glucose inhibits neural differentiation by excessive autophagy <em>via</em> peroxisome proliferator-activated receptor gamma
The high prevalence of prediabetes and diabetes globally has led to the widespread occurrence of severe complications, such as diabetic neuropathy, which is a result of chronic hyperglycemia. Studies have demonstrated that maternal diabetes can lead to neural tube defects by suppressing neurogenesis during neuroepithelium development. While aberrant autophagy has been associated with abnormal neuronal differentiation, the mechanism by which high glucose suppresses neural differentiation in stem cells remains unclear. Therefore, we developed a neuronal cell differentiation model of retinoic acid induced P19 cells to investigate the impact of high glucose on neuronal differentiation in vitro. Our findings indicate that high glucose (HG) hinders neuronal differentiation and triggers excessive. Furthermore, HG treatment significantly reduces the expression of markers for neurons (Tuj1) and glia (GFAP), while enhancing autophagic activity mediated by peroxisome proliferator-activated receptor gamma (PPARγ). By manipulating PPARγ activity through pharmacological approaches and genetically knocking it down using shRNA, we discovered that altering PPARγ activity affects the differentiation of neural stem cells exposed to HG. Our study reveals that PPARγ acts as a downstream mediator in high glucose-suppressed neural stem cell differentiation and that refining autophagic activity via PPARγ at an appropriate level could improve neuronal differentiation efficiency. Our data provide novel insights and potential therapeutic targets for the clinical management of gestational diabetes mellitus.
| Medienart: |
E-Artikel |
|---|
| Erscheinungsjahr: |
2023 |
|---|---|
| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:67 |
|---|---|
| Enthalten in: |
European journal of histochemistry : EJH - 67(2023), 2 vom: 11. Mai |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Pan, Yin [VerfasserIn] |
|---|
| Links: |
|---|
| Themen: |
|---|
| Anmerkungen: |
Date Completed 18.05.2023 Date Revised 02.06.2023 published: Electronic Citation Status MEDLINE |
|---|
| doi: |
10.4081/ejh.2023.3691 |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
NLM356737837 |
|---|
| LEADER | 01000naa a22002652 4500 | ||
|---|---|---|---|
| 001 | NLM356737837 | ||
| 003 | DE-627 | ||
| 005 | 20231226071113.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 231226s2023 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.4081/ejh.2023.3691 |2 doi | |
| 028 | 5 | 2 | |a pubmed24n1189.xml |
| 035 | |a (DE-627)NLM356737837 | ||
| 035 | |a (NLM)37170914 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a Pan, Yin |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a High glucose inhibits neural differentiation by excessive autophagy <em>via</em> peroxisome proliferator-activated receptor gamma |
| 264 | 1 | |c 2023 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ƒaComputermedien |b c |2 rdamedia | ||
| 338 | |a ƒa Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Date Completed 18.05.2023 | ||
| 500 | |a Date Revised 02.06.2023 | ||
| 500 | |a published: Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a The high prevalence of prediabetes and diabetes globally has led to the widespread occurrence of severe complications, such as diabetic neuropathy, which is a result of chronic hyperglycemia. Studies have demonstrated that maternal diabetes can lead to neural tube defects by suppressing neurogenesis during neuroepithelium development. While aberrant autophagy has been associated with abnormal neuronal differentiation, the mechanism by which high glucose suppresses neural differentiation in stem cells remains unclear. Therefore, we developed a neuronal cell differentiation model of retinoic acid induced P19 cells to investigate the impact of high glucose on neuronal differentiation in vitro. Our findings indicate that high glucose (HG) hinders neuronal differentiation and triggers excessive. Furthermore, HG treatment significantly reduces the expression of markers for neurons (Tuj1) and glia (GFAP), while enhancing autophagic activity mediated by peroxisome proliferator-activated receptor gamma (PPARγ). By manipulating PPARγ activity through pharmacological approaches and genetically knocking it down using shRNA, we discovered that altering PPARγ activity affects the differentiation of neural stem cells exposed to HG. Our study reveals that PPARγ acts as a downstream mediator in high glucose-suppressed neural stem cell differentiation and that refining autophagic activity via PPARγ at an appropriate level could improve neuronal differentiation efficiency. Our data provide novel insights and potential therapeutic targets for the clinical management of gestational diabetes mellitus | ||
| 650 | 4 | |a Journal Article | |
| 650 | 7 | |a Glucose |2 NLM | |
| 650 | 7 | |a IY9XDZ35W2 |2 NLM | |
| 650 | 7 | |a PPAR gamma |2 NLM | |
| 700 | 1 | |a Qiu, Di |e verfasserin |4 aut | |
| 700 | 1 | |a Chen, Shu |e verfasserin |4 aut | |
| 700 | 1 | |a Han, Xiaoxue |e verfasserin |4 aut | |
| 700 | 1 | |a Li, Ruiman |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t European journal of histochemistry : EJH |d 1997 |g 67(2023), 2 vom: 11. Mai |w (DE-627)NLM012612383 |x 2038-8306 |7 nnns |
| 773 | 1 | 8 | |g volume:67 |g year:2023 |g number:2 |g day:11 |g month:05 |
| 856 | 4 | 0 | |u http://dx.doi.org/10.4081/ejh.2023.3691 |3 Volltext |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a GBV_NLM | ||
| 951 | |a AR | ||
| 952 | |d 67 |j 2023 |e 2 |b 11 |c 05 | ||