Philipp E. Scherer
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View article: The complement pathway and the pathophysiology of fibroproliferative cutaneous scarring
The complement pathway and the pathophysiology of fibroproliferative cutaneous scarring Open
Fibroproliferative cutaneous pathologies such as hypertrophic scars and keloids have a high prevalence after burns and surgical interventions; however, their pathophysiology remains not fully understood. Here, we formulate a new pathophysi…
View article: The Role of COL6A3 in Tumorigenesis, Metastasis, Diagnosis, and Disease Management
The Role of COL6A3 in Tumorigenesis, Metastasis, Diagnosis, and Disease Management Open
Collagens comprise a large, diverse family of proteins that are abundantly expressed throughout most tissues. As a main component of the extracellular matrix (ECM), it is becoming increasingly appreciated how vital collagens are to tumor d…
View article: Leptin as a key driver for organ fibrogenesis
Leptin as a key driver for organ fibrogenesis Open
Leptin, a hormone primarily secreted by adipocytes, regulates energy balance and systemic metabolism through its interaction with the leptin receptor (LEPR). Beyond these functions, leptin signaling has been implicated in the pathogenesis …
View article: Acute kidney injury is associated with elevated urinary endotrophin
Acute kidney injury is associated with elevated urinary endotrophin Open
Endotrophin (ETP) is a molecule released during the formation of type VI collagen that may promote fibrosis and inflammation. Serum ETP is elevated in acute kidney injury (AKI) and associates with adverse outcomes. Urine ETP during AKI has…
View article: Serum endotrophin relates to blood pressure in young South Asian women but not White women: evidence of ethnic variation in its early vascular implications
Serum endotrophin relates to blood pressure in young South Asian women but not White women: evidence of ethnic variation in its early vascular implications Open
Background Endotrophin is a novel circulating fibroinflammatory protein that has recently been associated with cardiovascular disease (CVD) and all-cause mortality. However, little is known about its role early in the natural history of va…
View article: Metabolic dysregulation in the heart in obesity-associated HFpEF
Metabolic dysregulation in the heart in obesity-associated HFpEF Open
Background Obesity and hypertension are among the most prevalent comorbidities in heart failure with preserved ejection fraction (HFpEF). In addition to its relationship with hypertension in HFpEF, obesity is also strongly associated with …
View article: CRISPLD2, a novel insulin‐sensitizing adipokine that alters adipocyte size
CRISPLD2, a novel insulin‐sensitizing adipokine that alters adipocyte size Open
Objective Both obesity and adipose tissue fibrosis are associated with insulin resistance, which can improve with weight loss. We previously found increased adipocyte‐specific secretion of the novel adipokine CRISPLD2 during weight loss. I…
View article: Adipose Tissue as a Target for Precision Medicine Approaches in Childhood Obesity
Adipose Tissue as a Target for Precision Medicine Approaches in Childhood Obesity Open
Following the trends of the adult obesity epidemic, and worsened by school disruptions during the coronavirus disease 2019 pandemic, childhood obesity prevalence has reached unprecedented levels. The health implications for this generation…
View article: The potential of 4-Methylumbelliferone to be repurposed for treating liver fibrosis
The potential of 4-Methylumbelliferone to be repurposed for treating liver fibrosis Open
4-Methylumbelliferone (4-MU) is the active component of hymecromone, a choleretic and antispasmodic drug with an excellent safety profile. In rodent studies, high doses of 4-MU are also used to inhibit the production of hyaluronan (HA), a …
View article: Exoproteome of calorie-restricted humans identifies complement deactivation as an immunometabolic checkpoint reducing inflammaging
Exoproteome of calorie-restricted humans identifies complement deactivation as an immunometabolic checkpoint reducing inflammaging Open
Caloric restriction (CR) extends lifespan, yet the convergent immunometabolic mechanism of healthspan remains unclear. Using longitudinal plasma proteomics analyses in humans achieving 14% CR for 2 years, we identified that inhibition of t…
View article: Increase in Angiogenesis and Vascularization in Patient-Derived Endometriosis Tissue: Insights from a 3D In Vivo Model
Increase in Angiogenesis and Vascularization in Patient-Derived Endometriosis Tissue: Insights from a 3D In Vivo Model Open
Endometriosis is a gynecological disorder characterized by endometrial-like tissue outside the uterus. This study evaluates the vascularization and proliferation of human endometriosis and endometrium tissues engrafted onto the chorioallan…
View article: Exploring adipose tissue-derived extracellular vesicles in inter-organ crosstalk: Implications for metabolic regulation and adipose tissue function
Exploring adipose tissue-derived extracellular vesicles in inter-organ crosstalk: Implications for metabolic regulation and adipose tissue function Open
Intercellular and inter-organ communication systems are vital for tissue homeostasis and disease development, utilizing soluble bioactive molecules for signaling. The field of extracellular vesicle (EV) biology has rapidly expanded in rece…
View article: Loss of the alternative calcineurin variant CnAβ1 enhances brown adipocyte differentiation and drives metabolic overactivation through FoxO1 activation
Loss of the alternative calcineurin variant CnAβ1 enhances brown adipocyte differentiation and drives metabolic overactivation through FoxO1 activation Open
The alternative calcineurin A variant CnAβ1 has a unique C-terminal domain that provides it with distinct subcellular localization and mechanism of action different from other calcineurin isoforms. Here, we used mice lacking CnAβ1’s C-term…
View article: Regulation of the terminal complement cascade in adipose tissue for control of its volume, cellularity, and fibrosis
Regulation of the terminal complement cascade in adipose tissue for control of its volume, cellularity, and fibrosis Open
White adipose tissue (WAT) is a reservoir for various pathogens and their products, such as lipopolysaccharides. Therefore, it must be equipped with a defense mechanism connected with the activation of innate immunity. This explains the ph…
View article: ETP-Specific Knockout Mice Reveal Endotrophin as a Key Regulator of Kidney Fibrosis in Ischemia-Reperfusion Injury Models
ETP-Specific Knockout Mice Reveal Endotrophin as a Key Regulator of Kidney Fibrosis in Ischemia-Reperfusion Injury Models Open
Endotrophin (ETP), a cleavage product of the C5 domain of collagen VI α3 (COL6A3), plays a crucial role in extracellular matrix remodeling. Previously established Col6a3 knockout (KO) mouse models primarily reflect the consequences of COL6…
View article: Enhanced paracrine action of FGF21 in stromal cells delays thymic aging
Enhanced paracrine action of FGF21 in stromal cells delays thymic aging Open
Age-related thymic involution precedes aging of all other organs in vertebrates and initiates the process of declining T cell diversity, which leads to eventual immune dysfunction. Whether FGF21, a liver-derived pro-longevity hormone that …
View article: The adiponectin-PPARγ axis in hepatic stellate cells regulates liver fibrosis
The adiponectin-PPARγ axis in hepatic stellate cells regulates liver fibrosis Open
Hepatic stellate cells (HSCs) are key drivers of local fibrosis. Adiponectin, conventionally thought of as an adipokine, is also expressed in quiescent HSCs. However, the impact of its local expression on the progression of liver fibrosis …
View article: Adipogenin Dictates Adipose Tissue Expansion by Facilitating the Assembly of a Dodecameric Seipin Complex
Adipogenin Dictates Adipose Tissue Expansion by Facilitating the Assembly of a Dodecameric Seipin Complex Open
Adipogenin (Adig) is an evolutionarily conserved microprotein and is highly expressed in adipose tissues and testis. Here, we identify Adig as a critical regulator for lipid droplet formation in adipocytes. We determine that Adig interacts…
View article: Endotrophin as a Biomarker for Severe Acute Kidney Injury and Major Adverse Kidney Events
Endotrophin as a Biomarker for Severe Acute Kidney Injury and Major Adverse Kidney Events Open
Key Points Endotrophin (ETP), a circulating marker of fibroinflammation, is elevated in critically ill patients with AKI. ETP is independently associated with major adverse kidney events at hospital discharge. Sustained elevations of ETP a…
View article: IRE1α Mediates the Hypertrophic Growth of Cardiomyocytes Through Facilitating the Formation of Initiation Complex to Promote the Translation of TOP-Motif Transcripts
IRE1α Mediates the Hypertrophic Growth of Cardiomyocytes Through Facilitating the Formation of Initiation Complex to Promote the Translation of TOP-Motif Transcripts Open
BACKGROUND: Cardiomyocyte growth is coupled with active protein synthesis, which is one of the basic biological processes in living cells. However, it is unclear whether the unfolded protein response transducers and effectors directly take…
View article: Instrumental variable and colocalization analyses identify endotrophin and HTRA1 as potential therapeutic targets for coronary artery disease
Instrumental variable and colocalization analyses identify endotrophin and HTRA1 as potential therapeutic targets for coronary artery disease Open
Coronary artery disease (CAD) remains a leading cause of disease burden globally, and there is a persistent need for new therapeutic targets. Instrumental variable (IV) and genetic colocalization analyses can help identify novel therapeuti…
View article: Adipose Tissue Analysis Toolkit (ATAT) for automated analysis of adipocyte size and extracellular matrix in white adipose tissue
Adipose Tissue Analysis Toolkit (ATAT) for automated analysis of adipocyte size and extracellular matrix in white adipose tissue Open
Objective The pathological expansion of white adipose tissue (WAT) in obesity involves adipocyte hypertrophy accompanied by expansion of the collagen‐rich pericellular extracellular matrix (ECM) and development of crown‐like structures (CL…