Kisspeptins inhibit human airway smooth muscle proliferation

Borkar, Niyati A.; Ambhore, Nilesh Sudhakar; Kalidhindi, Rama Satyanarayana Raju; Pabelick, Christina M.; Prakash, Y. S.; Sathish, Venkatachalem

doi:10.1172/jci.insight.152762

Cited by 7 publications

(13 citation statements)

References 94 publications

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“…We showed differential expression of ASM Kp/KISS1R, with asthmatics showing the lowest expression of Kp and KISS1R. Moreover, we also demonstrated an anti-proliferative effect of Kp-10 by inhibiting PDGF-induced ASM cell proliferation in non-asthmatic and asthmatic human ASM [ 201 ]. The role of estrogen vs. testosterone in the regulation of Kp is not known and needs to be elucidated to determine any sex steroid signaling crosstalk responsible for sex differences in asthma.…”

Section: Sex Steroids and Structural Cells Of The Airwaymentioning

confidence: 97%

“…These uncertainties of a clear role of sex steroids in asthma warrant consideration of mechanisms independent or/dependent on sex steroids. In this regard, kisspeptins (Kp) are a crucial yet understudied peptide that could play an important role in asthma and inflammation [ 201 ]. With several reports studying the expression and function of Kp and its receptor, KISS1R, in cancer and other disease models, our study showed, for the first time, robust expression and function of Kp/KISS1R in human ASM [ 201 ].…”

Section: Sex Steroids and Structural Cells Of The Airwaymentioning

confidence: 99%

“…In this regard, kisspeptins (Kp) are a crucial yet understudied peptide that could play an important role in asthma and inflammation [ 201 ]. With several reports studying the expression and function of Kp and its receptor, KISS1R, in cancer and other disease models, our study showed, for the first time, robust expression and function of Kp/KISS1R in human ASM [ 201 ]. We showed differential expression of ASM Kp/KISS1R, with asthmatics showing the lowest expression of Kp and KISS1R.…”

Section: Sex Steroids and Structural Cells Of The Airwaymentioning

confidence: 99%

“…Fortunately, understanding the mechanisms by which sex steroids influence structural cells of the airways has garnered new interest with novel findings from researchers working on ASM, epithelial cells and fibroblast in the lungs [ 5 , 39 , 201 , 207 , 208 ]. Sex steroids influence structural cells of the airways and immune cells independently.…”

Section: Sex Steroids and Structural Cells Of The Airwaymentioning

confidence: 99%

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Sex Steroids Effects on Asthma: A Network Perspective of Immune and Airway Cells

Borkar

Combs

Sathish

2022

Cells

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A multitude of evidence has suggested the differential incidence, prevalence and severity of asthma between males and females. A compilation of recent literature recognized sex differences as a significant non-modifiable risk factor in asthma pathogenesis. Understanding the cellular and mechanistic basis of sex differences remains complex and the pivotal point of this ever elusive quest, which remains to be clarified in the current scenario. Sex steroids are an integral part of human development and evolution while also playing a critical role in the conditioning of the immune system and thereby influencing the function of peripheral organs. Classical perspectives suggest a pre-defined effect of sex steroids, generalizing estrogens popularly under the “estrogen paradox” due to conflicting reports associating estrogen with a pro- and anti-inflammatory role. On the other hand, androgens are classified as “anti-inflammatory,” serving a protective role in mitigating inflammation. Although considered mainstream and simplistic, this observation remains valid for numerous reasons, as elaborated in the current review. Women appear immune-favored with stronger and more responsive immune elements than men. However, the remarkable female predominance of diverse autoimmune and allergic diseases contradicts this observation suggesting that hormonal differences between the sexes might modulate the normal and dysfunctional regulation of the immune system. This review illustrates the potential relationship between key elements of the immune cell system and their interplay with sex steroids, relevant to structural cells in the pathophysiology of asthma and many other lung diseases. Here, we discuss established and emerging paradigms in the clarification of observed sex differences in asthma in the context of the immune system, which will deepen our understanding of asthma etiopathology.

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Section: Sex Steroids and Structural Cells Of The Airwaymentioning

confidence: 97%

Section: Sex Steroids and Structural Cells Of The Airwaymentioning

confidence: 99%

Section: Sex Steroids and Structural Cells Of The Airwaymentioning

confidence: 99%

Section: Sex Steroids and Structural Cells Of The Airwaymentioning

confidence: 99%

See 2 more Smart Citations

Sex Steroids Effects on Asthma: A Network Perspective of Immune and Airway Cells

Borkar

Combs

Sathish

2022

Cells

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“…This is further supported by in vivo studies using a mouse model of asthma showed an increased airway smooth muscle (ASM) layer thickness ( 11 - 13 ). Further, increased ASM mass due to increased ASMC proliferation, hypertrophy, and migration observed in asthmatics ( 6 , 14 , 15 ). All these evidences conflicts with the sentence mentioned in this review, “ bronchial biopsies from asthmatic and non-asthmatic patients have no significant difference in ASMCs proliferation ”.…”

mentioning

confidence: 96%

Molecular determinants of airway smooth muscle cells in health and disease

Ambhore¹,

Kumar²,

Sathish³

2022

Ann Transl Med

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Kisspeptin regulates airway hyperresponsiveness and remodeling in a mouse model of asthma

Borkar

Ambhore

Balraj

et al. 2023

The Journal of Pathology

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Asthma is a multifactorial disease of origin characterized by airway hyperresponsiveness (AHR) and airway remodeling. Several pieces of evidence from other pathologies suggest that Kisspeptins (Kp) regulate cell proliferation, migration, and invasion, mechanisms that are highly relevant to asthma. Our recent in vitro studies show Kp‐10 (active peptide of Kp), via its receptor, KISS1R, inhibits human airway smooth muscle cell proliferation. Here, we hypothesize a crucial role for Kp‐10 in regulating AHR and airway remodeling in vivo. Utilizing C57BL/6J mice, we assessed the effect of chronic intranasal Kp‐10 exposure on mixed allergen (MA)‐induced mouse model of asthma. MA‐challenged mice showed significant deterioration of lung function compared to those exposed to vehicle (DPBS); Kp‐10 treatment significantly improved the MA‐altered lung functions. Mice treated with Kp‐10 alone did not show any notable changes in lung functions. MA‐exposed mice showed a significant reduction in KISS1R expression as compared to vehicle alone. MA‐challenged mice showed significant alterations in immune cell infiltration in the airways and remodeling changes. Proinflammatory cytokines were significantly increased upon MA exposure, an effect abrogated by Kp‐10 treatment. Furthermore, biochemical and histological studies showed Kp‐10 exposure significantly reduced MA‐induced smooth muscle mass and soluble collagen in the lung. Overall, our findings highlight the effect of chronic Kp‐10 exposure in regulating MA‐induced AHR and remodeling. © 2023 The Pathological Society of Great Britain and Ireland.

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Kisspeptins inhibit human airway smooth muscle proliferation

Cited by 7 publications

References 94 publications

Sex Steroids Effects on Asthma: A Network Perspective of Immune and Airway Cells

Sex Steroids Effects on Asthma: A Network Perspective of Immune and Airway Cells

Molecular determinants of airway smooth muscle cells in health and disease

Kisspeptin regulates airway hyperresponsiveness and remodeling in a mouse model of asthma

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