Background: Patellofemoral Malalignment Versus Tissue Homeostasis

Human tissues, to maintain their architecture and function, respond to injuries by activating intricate biochemical and physical mechanisms that regulates intercellular communication crucial in maintaining tissue homeostasis. Coordination of the communication occurs through the activity of different actin cytoskeletal regulators, physically connected to extracellular matrix through integrins, generating a platform of biochemical and biomechanical signaling that is deregulated in cancer. Among the major pathways, a controller of cellular functions is the cytokine transforming growth factor β (TGFβ), which remains a complex and central signaling network still to be interpreted and explained in cancer progression. Here, we discuss the link between actin dynamics and TGFβ signaling with the aim of exploring their aberrant interaction in cancer.

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Autophagy Deficiency by Atg4B Loss Leads to Metabolomic Alterations in Mice

Metabolites ◽

10.3390/metabo11080481 ◽

2021 ◽

Vol 11 (8) ◽

pp. 481

Author(s):

Gemma G. Martínez-García ◽

Raúl F. Pérez ◽

Álvaro F. Fernández ◽

Sylvere Durand ◽

Guido Kroemer ◽

...

Keyword(s):

Skeletal Muscle ◽

Amino Acids ◽

Mammalian Cells ◽

Tissue Homeostasis ◽

In Vivo Studies ◽

Protective Mechanism ◽

Cardiac Damage ◽

Wide Range ◽

First Time

Autophagy is an essential protective mechanism that allows mammalian cells to cope with a variety of stressors and contributes to maintaining cellular and tissue homeostasis. Due to these crucial roles and also to the fact that autophagy malfunction has been described in a wide range of pathologies, an increasing number of in vivo studies involving animal models targeting autophagy genes have been developed. In mammals, total autophagy inactivation is lethal, and constitutive knockout models lacking effectors of this route are not viable, which has hindered so far the analysis of the consequences of a systemic autophagy decline. Here, we take advantage of atg4b−/− mice, an autophagy-deficient model with only partial disruption of the process, to assess the effects of systemic reduction of autophagy on the metabolome. We describe for the first time the metabolic footprint of systemic autophagy decline, showing that impaired autophagy results in highly tissue-dependent alterations that are more accentuated in the skeletal muscle and plasma. These changes, which include changes in the levels of amino-acids, lipids, or nucleosides, sometimes resemble those that are frequently described in conditions like aging, obesity, or cardiac damage. We also discuss different hypotheses on how impaired autophagy may affect the metabolism of several tissues in mammals.

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Existence of natural mouse IgG mAbs recognising epitopes shared by malondialdehyde acetaldehyde adducts and Porphyromonas gingivalis

Innate Immunity ◽

10.1177/1753425920981133 ◽

2021 ◽

Vol 27 (2) ◽

pp. 158-169

Author(s):

Mikael Kyrklund ◽

Heidi Kaski ◽

Ramin Akhi ◽

Antti E Nissinen ◽

Outi Kummu ◽

...

Keyword(s):

Porphyromonas Gingivalis ◽

Low Density Lipoprotein ◽

Physiological Role ◽

Density Lipoprotein ◽

Tissue Homeostasis ◽

Innate Immune ◽

Periodontal Pathogen ◽

First Line ◽

Germline Genes ◽

Innate Recognition

Natural Abs are produced by B lymphocytes in the absence of external Ag stimulation. They recognise self, altered self and foreign Ags, comprising an important first-line defence against invading pathogens and serving as innate recognition receptors for tissue homeostasis. Natural IgG Abs have been found in newborns and uninfected individuals. Yet, their physiological role remains unclear. Previously, no natural IgG Abs to oxidation-specific epitopes have been reported. Here, we show the cloning and characterisation of mouse IgG mAbs against malondialdehyde acetaldehyde (MAA)-modified low-density lipoprotein. Sequence analysis reveals high homology with germline genes, suggesting that they are natural. Further investigation shows that the MAA-specific natural IgG Abs cross-react with the major periodontal pathogen Porphyromonas gingivalis and recognise its principle virulence factors gingipain Kgp and long fimbriae. The study provides evidence that natural IgGs may play an important role in innate immune defence and in regulation of tissue homeostasis by recognising and removing invading pathogens and/or modified self-Ags, thus being involved in the development of periodontitis and atherosclerosis.

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Zelluläres Tauziehen: Wie Zellen auf mechanischen Stress antworten

BIOspektrum ◽

10.1007/s12268-021-1598-0 ◽

2021 ◽

Vol 27 (4) ◽

pp. 385-389

Author(s):

Kai Weissenbruch ◽

Marc Hippler ◽

Martin Bastmeyer

Keyword(s):

Tissue Homeostasis ◽

Physical Basis ◽

Technical Advance ◽

Molecular Scale ◽

Sense And Respond ◽

Intracellular Forces

AbstractThe ability of cells to sense and respond to extracellular forces is critical for cellular and tissue homeostasis. Tension or compression act on our body ubiquitously and cells respond to such mechanical cues by producing intracellular forces on their own. In this article, we briefly highlight the cellular and physical basis driving these phenomena and discuss our recent technical advance to stimulate and monitor the cellular mechanoresponse on a molecular scale.

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