Nuclear Genome-Encoded Long Noncoding RNAs and Mitochondrial Damage in Diabetic Retinopathy
Retinal mitochondria are damaged in diabetes-accelerating apoptosis of capillary cells, and ultimately, leading to degenerative capillaries. Diabetes also upregulates many long noncoding RNAs (LncRNAs), including Lnc<i>MALAT1</i> and Lnc<i>NEAT1</i>. These RNAs have more than...
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| Format: | Article |
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MDPI AG
2021-11-01
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| Series: | Cells |
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| Online Access: | https://www.mdpi.com/2073-4409/10/12/3271 |
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| author | Ghulam Mohammad Renu A. Kowluru |
| author_facet | Ghulam Mohammad Renu A. Kowluru |
| author_sort | Ghulam Mohammad |
| collection | DOAJ |
| description | Retinal mitochondria are damaged in diabetes-accelerating apoptosis of capillary cells, and ultimately, leading to degenerative capillaries. Diabetes also upregulates many long noncoding RNAs (LncRNAs), including Lnc<i>MALAT1</i> and Lnc<i>NEAT1</i>. These RNAs have more than 200 nucleotides and no open reading frame for translation. Lnc<i>MALAT1</i> and Lnc<i>NEAT1</i> are encoded by nuclear genome, but nuclear-encoded LncRNAs can also translocate in the mitochondria. Our aim was to investigate the role of Lnc<i>MALAT1</i> and Lnc<i>NEAT1</i> in mitochondrial homeostasis. Using human retinal endothelial cells, the effect of high glucose on Lnc<i>MALAT1</i> and Lnc<i>NEAT1</i> mitochondrial localization was examined by RNA fluorescence in situ hybridization. The role of these LncRNAs in mitochondrial membrane potential (by JC-I staining), mtDNA integrity (by extended length PCR) and in protective mtDNA nucleoids (by SYBR green staining) was examined in <i>MALAT1-</i> or <i>NEAT1-siRNA</i> transfected cells. High glucose increased Lnc<i>MALAT1</i> and Lnc<i>NEAT1</i> mitochondrial expression, and <i>MALAT1</i>-siRNA or <i>NEAT1</i>-siRNA ameliorated glucose-induced damage to mitochondrial membrane potential and mtDNA, and prevented decrease in mtDNA nucleoids. Thus, increased mitochondrial translocation of Lnc<i>MALAT1</i> or Lnc<i>NEAT1</i> in a hyperglycemic milieu plays a major role in damaging the mitochondrial structural and genomic integrity. Regulation of these LncRNAs can protect mitochondrial homeostasis, and ameliorate formation of degenerative capillaries in diabetic retinopathy. |
| first_indexed | 2024-03-10T04:25:59Z |
| format | Article |
| id | doaj.art-9ddaa4cb9209409fa4b5d6ad5e738805 |
| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-10T04:25:59Z |
| publishDate | 2021-11-01 |
| publisher | MDPI AG |
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| series | Cells |
| spelling | doaj.art-9ddaa4cb9209409fa4b5d6ad5e7388052023-11-23T07:35:28ZengMDPI AGCells2073-44092021-11-011012327110.3390/cells10123271Nuclear Genome-Encoded Long Noncoding RNAs and Mitochondrial Damage in Diabetic RetinopathyGhulam Mohammad0Renu A. Kowluru1Department of Ophthalmology, Visual & Anatomical Sciences, Wayne State University, Detroit, MI 48201, USAKresge Eye Institute, 4717 St. Antoine, Detroit, MI 48201, USARetinal mitochondria are damaged in diabetes-accelerating apoptosis of capillary cells, and ultimately, leading to degenerative capillaries. Diabetes also upregulates many long noncoding RNAs (LncRNAs), including Lnc<i>MALAT1</i> and Lnc<i>NEAT1</i>. These RNAs have more than 200 nucleotides and no open reading frame for translation. Lnc<i>MALAT1</i> and Lnc<i>NEAT1</i> are encoded by nuclear genome, but nuclear-encoded LncRNAs can also translocate in the mitochondria. Our aim was to investigate the role of Lnc<i>MALAT1</i> and Lnc<i>NEAT1</i> in mitochondrial homeostasis. Using human retinal endothelial cells, the effect of high glucose on Lnc<i>MALAT1</i> and Lnc<i>NEAT1</i> mitochondrial localization was examined by RNA fluorescence in situ hybridization. The role of these LncRNAs in mitochondrial membrane potential (by JC-I staining), mtDNA integrity (by extended length PCR) and in protective mtDNA nucleoids (by SYBR green staining) was examined in <i>MALAT1-</i> or <i>NEAT1-siRNA</i> transfected cells. High glucose increased Lnc<i>MALAT1</i> and Lnc<i>NEAT1</i> mitochondrial expression, and <i>MALAT1</i>-siRNA or <i>NEAT1</i>-siRNA ameliorated glucose-induced damage to mitochondrial membrane potential and mtDNA, and prevented decrease in mtDNA nucleoids. Thus, increased mitochondrial translocation of Lnc<i>MALAT1</i> or Lnc<i>NEAT1</i> in a hyperglycemic milieu plays a major role in damaging the mitochondrial structural and genomic integrity. Regulation of these LncRNAs can protect mitochondrial homeostasis, and ameliorate formation of degenerative capillaries in diabetic retinopathy.https://www.mdpi.com/2073-4409/10/12/3271diabetic retinopathylong noncoding RNAmitochondria |
| spellingShingle | Ghulam Mohammad Renu A. Kowluru Nuclear Genome-Encoded Long Noncoding RNAs and Mitochondrial Damage in Diabetic Retinopathy Cells diabetic retinopathy long noncoding RNA mitochondria |
| title | Nuclear Genome-Encoded Long Noncoding RNAs and Mitochondrial Damage in Diabetic Retinopathy |
| title_full | Nuclear Genome-Encoded Long Noncoding RNAs and Mitochondrial Damage in Diabetic Retinopathy |
| title_fullStr | Nuclear Genome-Encoded Long Noncoding RNAs and Mitochondrial Damage in Diabetic Retinopathy |
| title_full_unstemmed | Nuclear Genome-Encoded Long Noncoding RNAs and Mitochondrial Damage in Diabetic Retinopathy |
| title_short | Nuclear Genome-Encoded Long Noncoding RNAs and Mitochondrial Damage in Diabetic Retinopathy |
| title_sort | nuclear genome encoded long noncoding rnas and mitochondrial damage in diabetic retinopathy |
| topic | diabetic retinopathy long noncoding RNA mitochondria |
| url | https://www.mdpi.com/2073-4409/10/12/3271 |
| work_keys_str_mv | AT ghulammohammad nucleargenomeencodedlongnoncodingrnasandmitochondrialdamageindiabeticretinopathy AT renuakowluru nucleargenomeencodedlongnoncodingrnasandmitochondrialdamageindiabeticretinopathy |