T-Cadherin Modulates Adipogenic Differentiation in MesenchymalStem Cells: Insights into Ligand Interactions

Sysoeva, V.; Semina, E.; Klimovich, P.; Kulebyakin, K.; Dzreyan, V.; Sotskaya, E.; Shchipova, A.; Popov, V.; Shilova, A.; Brodsky, I.; Khabibullin, N.; Voloshin, N.; Tkachuk, V.; Rubina, K.

Авторы: Sysoeva Veronika, Semina Ekaterina, Klimovich Polina, Kulebyakin Konstantin, Dzreyan Valentina, Sotskaya Ekaterina, Shchipova Anna, Popov Vladimir, Shilova Anna, Brodsky Ilya, Khabibullin Nikita, Voloshin Nikita, Tkachuk Vsevolod, Rubina Kseniya
Журнал: Frontiers in Cell and Developmental Biology
Том: 12
Год издания: 2024
Издательство: Frontiers Media S.A.
Местоположение издательства: Lausanne, Switzerland
DOI: 10.3389/fcell.2024.1446363
Аннотация: T-cadherin, a non-canonical member of the cadherin superfamily, was initially identified forits involvement in homophilic recognition within the nervous and vascular systems. Apart from itsadhesive function, T-cadherin acts as a receptor for two ligands: LDL, contributing to atherogenicprocesses, and HMW adiponectin, a hormone with well-known cardiovascular protective properties.However, the precise role of T-cadherin in adipose tissue remains elusive. Previously, we generatedCdh13∆Exon3 mice lacking exon 3 in the Cdh13 gene, which encodes the T-cadherin protein, andcharacterized their phenotype. In this study, we demonstrate for the first time that T-cadherininfluences the adipogenic differentiation of MSCs. The presence of T-cadherin dictates distinctmorphological characteristics in MSCs. Lack of T-cadherin leads to spontaneous differentiation intoadipocytes with the formation of large lipid droplets. T-cadherin-deficient cells (T-/- MSCs) exhibitan enhanced adipogenic potential upon induction with differentiating factors. Western Blot, ELISAassays, and rescue experiments collectively corroborate the conclusion that T-/- MSCs arepredisposed toward adipogenic differentiation.We carried out an original comparative analysis to explore the effects of T-cadherin ligands on lipiddroplet accumulation. LDL stimulate adipogenic differentiation, while T-cadherin expressionmitigates the impact of LDL on lipid droplet accumulation. We also examined the effects of both lowmolecular weight (LMW) and high molecular weight (HMW) adiponectin on lipid dropletaccumulation relative to T-cadherin. LMW adiponectin suppressed lipid droplet accumulationindependently of T-cadherin, while the absence of T-cadherin enhanced susceptibility to thesuppressive effects of HMW adiponectin on adipogenesis. These findings shed light on the role of T-cadherin in adipogenic differentiation and suggest an interplay with other receptors, such as LDLRand AdipoRs, wherein downstream signaling may be modulated through lateral interactions with T-cadherin.
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