Expression of transgene encoded TGF-beta in islets prevents autoimmune diabetes in NOD mice by a local mechanism - PubMed (original) (raw)
. 2002 Aug-Sep;19(1-2):9-22.
doi: 10.1006/jaut.2002.0599.
Affiliations
- PMID: 12367555
- DOI: 10.1006/jaut.2002.0599
Expression of transgene encoded TGF-beta in islets prevents autoimmune diabetes in NOD mice by a local mechanism
Iqbal S Grewal et al. J Autoimmun. 2002 Aug-Sep.
Abstract
To analyse the effects of TGF-beta in insulin dependent diabetes mellitus (IDDM), we have developed non-obese diabetic (NOD) transgenic mice expressing TGF-beta under the control of the rat insulin II promoter. Pancreata of TGF-beta transgenic mice were roughly one twentieth of the size of pancreata of wild-type NOD mice and showed small clusters of micro-islets rather than normal adult islets. However, these islets produced sufficient levels of insulin to maintain normal glucose levels and mice were protected from the diabetes, which developed in their negative littermates. A massive fibrosis was seen in the transgenic pancreata that was accompanied with infiltration of mononuclear cells that decreased with age. Interestingly, these mice showed normal anti-islet immune response in their spleens and remained susceptible to adoptive transfer of IDDM by mature cloned CD8 effector cells. TUNEL assays revealed increased apoptosis of invading cells when compared to non-transgenic NOD mice. Taken together, these results suggest that TGF-beta protects islets by a local event.
Similar articles
- Local expression of transgene encoded TNF alpha in islets prevents autoimmune diabetes in nonobese diabetic (NOD) mice by preventing the development of auto-reactive islet-specific T cells.
Grewal IS, Grewal KD, Wong FS, Picarella DE, Janeway CA Jr, Flavell RA. Grewal IS, et al. J Exp Med. 1996 Nov 1;184(5):1963-74. doi: 10.1084/jem.184.5.1963. J Exp Med. 1996. PMID: 8920883 Free PMC article. - Abrogation of autoimmune diabetes in nonobese diabetic mice and protection against effector lymphocytes by transgenic paracrine TGF-beta1.
Moritani M, Yoshimoto K, Wong SF, Tanaka C, Yamaoka T, Sano T, Komagata Y, Miyazaki J, Kikutani H, Itakura M. Moritani M, et al. J Clin Invest. 1998 Aug 1;102(3):499-506. doi: 10.1172/JCI2992. J Clin Invest. 1998. PMID: 9691086 Free PMC article. - An update on cytokines in the pathogenesis of insulin-dependent diabetes mellitus.
Rabinovitch A. Rabinovitch A. Diabetes Metab Rev. 1998 Jun;14(2):129-51. doi: 10.1002/(sici)1099-0895(199806)14:2<129::aid-dmr208>3.0.co;2-v. Diabetes Metab Rev. 1998. PMID: 9679667 Review. - Genetic engineering of insulin expression in nonislet cells: implications for beta-cell replacement therapy for insulin-dependent diabetes mellitus.
Lipes MA, Davalli AM, Cooper EM. Lipes MA, et al. Acta Diabetol. 1997 Mar;34(1):2-5. doi: 10.1007/s005920050056. Acta Diabetol. 1997. PMID: 9134049 Review.
Cited by
- Circulating hsa-miR-320a and its regulatory network in type 1 diabetes mellitus.
Nizam R, Malik MZ, Jacob S, Alsmadi O, Koistinen HA, Tuomilehto J, Alkandari H, Al-Mulla F, Thanaraj TA. Nizam R, et al. Front Immunol. 2024 Oct 11;15:1376416. doi: 10.3389/fimmu.2024.1376416. eCollection 2024. Front Immunol. 2024. PMID: 39464889 Free PMC article. - Triphenyl Phosphate Alters Methyltransferase Expression and Induces Genome-Wide Aberrant DNA Methylation in Zebrafish Larvae.
Negi CK, Bláhová L, Phan A, Bajard L, Blaha L. Negi CK, et al. Chem Res Toxicol. 2024 Sep 16;37(9):1549-1561. doi: 10.1021/acs.chemrestox.4c00223. Epub 2024 Aug 29. Chem Res Toxicol. 2024. PMID: 39205618 Free PMC article. - Receptors and Signaling Pathways Controlling Beta-Cell Function and Survival as Targets for Anti-Diabetic Therapeutic Strategies.
Dalle S, Abderrahmani A. Dalle S, et al. Cells. 2024 Jul 24;13(15):1244. doi: 10.3390/cells13151244. Cells. 2024. PMID: 39120275 Free PMC article. Review. - Combination of anti-CD25 antibody and poly I:C treatment in pregnant NOD mice may be used as 'pregnancy-related' type 1 diabetes model.
Shimada A, Toda K, Inoue I, Yamada T, Oikawa Y. Shimada A, et al. J Diabetes Investig. 2022 Sep;13(9):1489-1495. doi: 10.1111/jdi.13829. Epub 2022 May 26. J Diabetes Investig. 2022. PMID: 35533022 Free PMC article. - Role of TGF-Beta Signaling in Beta Cell Proliferation and Function in Diabetes.
Wang HL, Wang L, Zhao CY, Lan HY. Wang HL, et al. Biomolecules. 2022 Feb 26;12(3):373. doi: 10.3390/biom12030373. Biomolecules. 2022. PMID: 35327565 Free PMC article. Review.
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Medical
Molecular Biology Databases
Research Materials