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Terminal differentiation of keratinocytes was damaged in type 2 diabetic mice
Takeshi Takayanagi1, Hiroyuki Hirai1, Yohei Asada1
1Department of Endocrinology, Diabetes and Metabolism, Fujita Health University, 1-98 Dengakugakubo, Kutsukake, Toyoake, Aichi, 470-1192, Japan.
Aims:
Although skin manifestations are common in diabetic patients, its characteristics are poorly identified. This study explored the differentiation process of keratinocytes in type 2 diabetes mellitus (T2DM) in vivo.
Methods:
Back skin of T2DM model KKAy/TaJcl mice (KKAy) and C57BL/6JJcl mice (control) aged 8 and 12 weeks was used. The mRNA expression of differentiation markers of keratinocytes was measured by quantitative real-time polymerase chain reaction (qRT-PCR). The expression of each marker in situ was examined immunohistochemically.
Results:
KKAy mice showed hyperglycemia versus control mice. The histological findings showed increased thickness and structural impairment of epidermal tissue in KKAy mice. The qRT-PCR revealed that the expression of integrin beta 1 and keratin 14 in KKAy and control mice was identical. However, the expression of involucrin at 8 weeks, keratin 10 at 12 weeks, and filaggrin and loricrin at 8 and 12 weeks was decreased in KKAy mice. Immunohistochemical findings showed that filaggrin was markedly decreased in KKAy mice, though Ki-67 remained unchanged.
Conclusion:
The terminal differentiation process was impaired in the diabetic skin, while keratinocyte proliferation was preserved. Damaged terminal differentiation of keratinocytes may contribute to impairment of the skin barrier function in diabetic dermatoses.
Insights
Type 2 diabetes mellitus (T2DM) impairs skin barrier function by disrupting keratinocyte differentiation. This study in mice reveals reduced expression of key differentiation markers, suggesting a mechanism for diabetic dermatoses.
Area of Science:
- Dermatology
- Endocrinology
- Molecular Biology
Background:
- Skin manifestations are frequent in patients with type 2 diabetes mellitus (T2DM), but their specific characteristics remain poorly understood.
- Understanding keratinocyte behavior in T2DM is crucial for addressing associated dermatological complications.
Purpose of the Study:
- To investigate the in vivo differentiation process of keratinocytes in a mouse model of type 2 diabetes mellitus.
- To identify specific molecular changes in keratinocyte differentiation associated with T2DM.
Main Methods:
- Utilized KKAy/TaJcl mice (T2DM model) and C57BL/6JJcl mice (control) at 8 and 12 weeks of age.
- Quantified mRNA expression of keratinocyte differentiation markers using quantitative real-time polymerase chain reaction (qRT-PCR).
- Examined marker expression in situ via immunohistochemistry.
Main Results:
- KKAy mice exhibited hyperglycemia and showed increased epidermal thickness with structural impairment compared to controls.
- While integrin beta 1 and keratin 14 expression were similar, KKAy mice displayed decreased expression of involucrin, keratin 10, filaggrin, and loricrin.
- Immunohistochemistry confirmed a marked decrease in filaggrin expression in KKAy mice, with no change in keratinocyte proliferation marker Ki-67.
Conclusions:
- The terminal differentiation of keratinocytes is impaired in diabetic skin, indicating a specific molecular defect in T2DM.
- Keratinocyte proliferation remains preserved, suggesting the defect lies in terminal differentiation rather than cell division.
- Impaired terminal differentiation of keratinocytes likely contributes to the compromised skin barrier function observed in diabetic dermatoses.
